cord-000149-dp8971im 2009 cord-000224-2lz03oqb 2010 METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. We hypothesized that recapitulating endogenous expression of the entire class II antigen presentation pathway in producer cells via expression of CIITA would restore infectious virus release and provide a more physiologically relevant model for HIV-1 assembly studies. Virus release, both infectious and particle titers) were reduced when cells were transfected with either HLA-DR or other components of the MHC class II antigen presentation pathway ( Figure S2 ), confirming a correlation between Gag retention and reduced virus titers in the presence of HLA-DR, as previously demonstrated [8] . Together, these data suggest CIITA has two effects on the HIV replicative cycle in producer cells, both of which are independent of the MHC II antigen processing pathway; i) it does not induce HLA-DR, mediated intracellular retention of Gag and ii) it increases the infectivity of HIV virions. cord-000479-u87eaaj8 2011 cord-000488-x5ardo5j 2011 cord-000695-g5sum116 2012 For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. The NP protein sequence of H5N1 isolate A/Goose/Gongdong/1/96 (H5N1) was downloaded from the UniProt database (UniProtID: NCAP_I96A0) and automatically parsed as octapep-tides or nonapeptides using a computer program, which was developed in our laboratory, based on the peptide-binding motifs of chicken MHC class I molecules belonging to the B4, B12, B15, and B19 haplotypes [22] . Using a motif combined with a structure-based method, 25 potential T cell epitope peptides were predicted in the H5N1 AIV NP in chickens of B4, B12, B15, and B19 haplotypes. First, this is the first study to determine the structural characteristics of the peptide-binding domains of chicken MHC class I molecules belonging to the B4, B12, B15, and B19 haplotypes using a combined motif-structure method to predict T cell epitopes in chickens. cord-000871-ej0e1c4d 2013 cord-001674-tp4o7fxx 2015 cord-002463-qhtj1pef 2017 cord-002686-zzongyfa 2017 cord-003270-vu9b5a14 2018 In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens'' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores. cord-003472-ml4pbewf 2019 cord-004518-jd1wxobz 2007 cord-004975-4c23d77d 1997 cord-005330-4k7hc1ww 2005 In this review, we attempt to summarize the existing knowledge on T-cell effects and-if availablepotential ways of its therapeutic modification in Rasmussen encephalitis (RE), paraneoplastic encephalomyelitis (PEM), and virus encephalitides. This assumption is based on the neuropathological findings of elements of a cytotoxic T-cell attack within the brains of affected people (Bernal et al., 2002) but also on some other observations regarding anti-Yo, anti-Hu, and anti-Ma syndromes and their respective antigens, cerebellar degenerationrelated protein 2 (cdr2), HuD, and PNMA1. The most prominent evidence for a pathogenetically relevant contribution of T-cells to PEM comes from studies on patients with anti-Yo positive paraneoplastic cerebellar degeneration. study on TCR Vβ families of T-lymphocytes within the brains of anti-Hu positive patients (autopsy specimens) providing evidence for an oligoclonal expansion of CD8 + T-cells are concordant with this concept (Voltz et al., 1998) . Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration Modelling paraneoplastic CNS disease: T-cells specific for the onconeuronal antigen PNMA1 mediate autoimmune encephalomyelitis in the rat cord-005393-rhji4io9 1997 cord-005400-50lmj4op 2005 cord-005550-qrrdi667 2007 title: Non-neutral evolution of the major histocompatibility complex class II gene DRB1 in the sac-winged bat Saccopteryx bilineata Thus, the data are consistent with the hypothesis that recombination gives rise to new alleles at the DRB locus of the sac-winged bat, and these are maintained in the population through balancing selection. We analysed the antigen-binding region of the MHC class II gene DRB of the sac-winged bat Saccopteryx bilineata by sequencing cloned PCR products. In this study, we describe the genetic diversity within exon 2 of the MHC class II gene DRB, and discuss the role of recombination and selection in generating and maintaining high levels of genetic diversity in colonies of the sac-winged bat. Variation at the DRB1 locus; evidence of recombination/ gene conversion Ten alleles were detected within the main sample of 79 individuals from the La Selva population. cord-005953-5z89yeb6 2008 Die anderen beiden Gruppen zeigten zwar in Hinblick auf die Wandstärken einen positiven Effekt, hinsichtlich der Herzfunktion konnten sie jedoch bei bereits deutlich erniedrigten Funktionswerten zum Baseline-Zeitpunkt lediglich stabilisiert werden (Reduktion der Wandstärke nach 3 Jahren ERT: Gruppe wenig Fibrose= 10 mm; Gruppe viel Fibrose= 12 mm) Schlussfolgerung: Die Enzymersatztherapie ist eine effektive Langzeitbehandlung bei Patienten mit Fabry Kardiomyopathie. Der Einfluss der sauren Sphingomyelinase auf die Expression von Matrix-Metalloproteinase-1 in intestinalen Epithelzellen und Fibroblasten Background: The calcineurin (Cn)/NF-AT signaling cascade takes a crucial role during T-cell activation and the development of myocardial hypertrophy. Effective and safe reduction of blood pressue by the combination of amlodipine 5/valsartan 160 mg in patients with hypertension and metabolic risk factors not controlled by amlodipine 5 mg or felodipine 5 mga subanalysis of the express-m trial Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and frequently occurs in patients with coronary heart disease. cord-007275-emmoeuqd 2007 title: An Impaired Breeding Phenotype in Mice with a Genetic Deletion of Beta-2 Microglobulin and Diminished MHC Class I Expression: Role in Reproductive Fitness(1) Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals, including its association with major histocompatibility complex (MHC) Class I gene products. Here we report the results of a longitudinal study of the reproductive performance of a genetically modified B2m deficient mouse strain with low MHC Class I expression. In the course of experiments designed to generate mouse embryos for gene transcription studies and immuno-detection of MHC products [50] [51] , we consistently observed an impaired reproductive capacity in the B2m deficient mice. Therefore, a possible mechanism operating in the B2m-deficient mice is the absence of secreted MHC class I products, and thus the absence of mating signals resulting in impaired breeding. cord-007301-5m269nzi 2007 cord-007603-27m9wz0i 2002 cord-007621-rapinodd 2002 Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. To determine the steady-state level of mRNA for class II, Northern blot analysis was performed using a eDNA probe for murine class Ii genes (E-a), with total RNA isolated from cultured astrocytes. The duration of protein synthesis required to allow expression of the class II MHC gene in astrocytes was examined in cells that were pretreated with IFN-y or IFN-7/TNF-a for different lengths of time prior to the addition of CHX. In this study we have shown that primary neonatal rat astrocytes, upon stimulation with IFN-~,, express mRNA transcripts for class II MHC genes, and that TNF-a enhances the expression of IFN-~,-induced class II mRNA. The expression of class II mRNA was completely inhibited when CHX was included with IFN-~, and IFN-''t/TNF-~ treatment, indicating that newly synthesized protein is required for astrocyte class II MHC gene expression. cord-007636-kfd0wqdx 2002 cord-007654-lchdm4xr 2002 cord-007851-v6h1yro7 2020 cord-008523-avkgldnp 2004 cord-009567-osstpum6 2008 Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers. cord-009570-djxoiytq 2001 Both clinical and experimental evidence supports the hypothesis that immune mechanisms are involved in the pathogenesis of inflammatory demyelination in multiple sclerosis (MS) and that autoreactive T lymphocytes initiate the process of central nervous system (CNS) myelin damage. This disease model has provided insight into the pathogenic "steps" that may be relevant to MS, including (1) genetic susceptibility, (2) priming and activation of myelin-specific T cells, (3) interaction of autoreactive T cells with endothelium and migration into the CNS, and (4) recognition of myelin antigens and initiation of inflammatory or demyelinating damage (Fig 1) . 44, 45 Molecular mimicry motifs that would satisfy both MHC binding and recognition by specific TCR were used by Wucherpfennig and Strominger 46 to identify microbial peptides that were effective in activating three MBPspecific T-cell clones (TCCs) derived from MS patients (Table 1) . Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein cord-010500-ajmj2hyj 2008 The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. As an illustration of the varying levels of MHC polymorphism in cattle and moose, a blot with bovine PVuII digests hybridized with the same human DQB probe as employed in the present study is shown in Fig. I@) . There is a clear difference between the moose and cattle as regards their degrees of MHC polymorphism in relation to their genome-wide genetic variability measured by DNA fingerprinting. cord-010508-jtbxefm4 2020 cord-010640-s1oqphvn 2020 cord-011173-c1i0a92f 2019 Whereas the presence and expression of neoantigen proteins can be identified through sequencing of the tumour exome, the neoepitopes presented by MHC II molecules must be either discovered empirically using expensive and time-consuming mass spectrometry (MS) techniques 4 or predicted using software-based estimations of peptide-MHC II binding affinity. The deconvoluted peptidomic datasets were then used to train a prediction algorithm, MixMHC2pred, which returns an MHC II binding score for a given peptide sequence and HLA-D allele. The efficacy of such neoantigen-based immunotherapies will be dependent on the identification of a sufficient number of MHC II-binding peptides to stimulate CD4 + T cell responses. Both MARIA and MixMHC2pred have the potential to make personalized neoantigen-based therapies more accessible to patients, including patients with tumours harbouring fewer mutations, by identifying more MHC II-binding epitopes to which CD4 + T cells can respond within each patient''s pool of putative neoantigens. cord-013093-aa4cf44u 2020 The detailed and unbiased characterization of HA-reactive memory and naive CD4 + T cell repertoires, paralleled by a deep analysis of the naturally presented repertoire of MHC-II-binding HA peptides by mass spectrometry (MS)-based immunopeptidomics, allowed us to shed new light on the factors governing CD4 + T cell clonal selection and immunodominance to influenza HA in humans. We then selected a large number of H1-HA-specific T cell clones derived from naive or memory T cells of donor HD1 and determined their functional avidity by measuring the proliferative response to autologous monocytes pulsed with different concentrations of the H1-HA peptides or H1-HA protein, which need processing for presentation on MHC-II molecules. cord-013315-plptulfb 2020 The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The class I MHC epitopes as of Figure 3 are further aligned against both the mycobacteria and cow databases to assess the specificity of the predicted epitope sequences for MAP. To prove selected epitopes as suitable candidates for the unbiased diagnosis of MAP infection, we aligned the peptides sequences against a database comprising the closest taxonomically-related bacteria. Selected peptide sequences of the immunoreactive proteins were searched against the NCBInr database restricted to Mycobacterium avium subsp. Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome cord-013590-pkm81fq1 2020 cord-016594-lj0us1dq 2012 cord-017296-jdp8kgg5 2008 cord-017629-fuv157f1 2008 cord-017819-85x0juiw 2006 It is, therefore, not surprising that corticosteroid level is measured in many studies in ecology and conservation biology that have evaluated the effect of different environmental and human perturbations on the stress level of wild animals (Creel et al. In contrast, widespread host species that live in high density are exposed to a wide range of parasite species that may affect drastically the population dynamics of these carnivores, suggesting that macroparasites may regulate them at least locally. Interestingly, Allee effects and parasitism have several features in common that are of interest when studying population dynamics in conservation biology (Deredec 2005) . Invasive host species have another advantage if they have invested in strong immune defences in their natural range, which may then subsequently confer a better capacity to control parasites that they may acquire in the introduced habitat. cord-018034-gx5c9mk8 2006 cord-021079-m6nbs2c0 2004 cord-021693-odfxkfu7 2007 Data from animal studies in the EAE model established that CD4 + Thl cells specific to myelin antigens can play a central role in the induction and progression of autoimmune demyelinating disease [2, 3] . In examining the immune response to MBP, we found that complementary mutations in an antigenic peptide allow for cross-reactivity of autoreacfive T cell clones that may be related to shifts of the TCR structure itself [11] . The new knowledge obtained from this study was 1) that of highly degenerative recognition of peptides by autoreactive CD4 § T cells, including identification of stimulatory ligands not sharing a single amino acid in corresponding positions with the antigen used to establish the T cell clone and 2) the identification of more potent agonistic peptides than cognate self-peptide. Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein Cross-reactive human autoreactive T-ceU receptor responses to altered peptide ligands presented by different MHC class II molecules cord-022142-d4yxgv83 2016 A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter highlights the repertoire of non-viral, nanosized polymeric DNA delivery systems (polyplexes) available to achieve effi cient gene transfer into DCs for immunotherapeutic applications in cancer therapy. With respect to clinical translation, effi cacious non-viral gene delivery into DCs will depend on the combination of intelligent material design, the appropriate tumor specifi c antigen-encoding DNA and immuno-stimulatory molecules to promote DC maturation and activation. cord-022395-rk31pwoa 2012 Acute and chronic relapsing EAE can be induced in laboratory animals by an injection of CNS tissue, CNS myelin, myelin basic protein, or more recently, T-cell lines specific for nervous system antigens. Infection with mouse hepatitis virus (MHV), has been shown to block expression of MHC molecules on murine cerebral endothelial cells (see later discussion) (Joseph et al., 1991) . Until recently, the HLA Class I molecules were thought to be the primary, if not the only, HLA recognition structure for CTLs. Studies of measles and Epstein-Barr virus (EBV) infection suggest that HLA Class II molecules can also serve as recognition sites, further expanding the potential action of CTLs. Viral antigens recognized by CTLs have also been expanded beyond the traditional cell surface molecules (Braciale and Braciale, 1986) . The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of virus and lead to CNS disease. Immune response gene products (la antigens) on glial and endothelial cells in virus-induced demyelination cord-022888-dnsdg04n 2009 Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cord-023055-ntbvmssh 2004 Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. cord-023143-fcno330z 2004 cord-023724-5at0rhqk 2015 The problems plant viruses face in initiating infections of host cells have already been described (Chapter 4), as has the fact that no known plant virus employs a specific cellular receptor of the types that animal and bacterial viruses use to attach to cells. There are probably many different mechanisms involved in systemic resistance, but in general terms there is a tendency of these processes to increase local necrosis when substances such as proteases and peroxidases are produced by the plant to destroy the virus and to prevent its spread and subsequent systemic infection. Virus-resistant plants have been created by the production of transgenic plants expressing recombinant virus proteins or nucleic acids which interfere with virus replication without producing the pathogenic consequences of infection, for example: I Virus coat proteins, which have a variety of complex effects, including inhibition of virus uncoating and interference of expression of the virus at the level of RNA ("gene silencing" by "untranslatable" RNAs), I Intact or partial virus replicases which interfere with genome replication, I Antisense RNAs, I Defective virus genomes, I Satellite sequences (see Chapter 8), I Catalytic RNA sequences (ribozymes), I Modified movement proteins. cord-025523-6ttps1nx 2020 title: Cross-Domain Authorship Attribution Using Pre-trained Language Models An especially challenging but very realistic scenario is cross-domain attribution where texts of known authorship (training set) differ from texts of disputed authorship (test set) in topic or genre. Recently, the use of pre-trained language models (e.g., BERT, ELMo, ULM-FiT, has been demonstrated to obtain significant gains in several text classification tasks including sentiment analysis, emotion classification, and topic classification [2, 7, 13, 14] . This method is based on a character-level recurrent (RNN) neural network language model and a multiheaded classifier (MHC) [1] . We examine the use of pre-trained language models (e.g., BERT, ELMo, ULMFiT, GPT-2) in AA and the potentials of MHC. Based on Bagnall''s model [1] , originally proposed for authorship verification, we compare the performance when we use either the original characterlevel RNN trained from scratch in the small-size AA corpus or pre-trained tokenbased language models obtained from general-domain corpora. cord-028945-p3hhd5ed 2020 cord-259669-fod4xkd7 2008 Being strategically located at sites of pathogen entry, such as mucosal surfaces and Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. Altogether, the co-expression of CD172a and CD1 along with relatively high levels of both CD80/86 and MHC class II represent phenotypic characteristics of porcine MoDC but no marker clearly differentiating them from monocyte-derived macrophages has been identified. cord-260485-o5wpcxdp 2018 cord-264401-9ogs55xr 2020 cord-267266-0lybzcz7 2000 These ''danger'' or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. The DC are sensitive to a wide range of these stimuli that serve not only to activate innate immunity via the release of chemokines and proinflammatory mediators, but also trigger DC migration towards local lymphoid tissue in order to generate antigen-specific (adaptive) immunity. 37, 38 For the Langerhans cell, activation is also accompanied by the loss of specific markers, such as cutaneous lymphocyte antigen (CLA) and Birbeck granules, along with altered surface expression of cell adhesion molecules that facilitate movement into the afferent lymph. 138 Flt-3 is able to induce protective antitumour immunity in some animal models, 139, 140 which is thought to be a consequence of increased presentation of tumour antigens combined with increased NK cell activity. FcγR-mediated induction of dendritic cell maturation and MHC class I-restricted antigen presentation after immune complex internalisation cord-269917-j0t8rjkc 2020 cord-273906-s7l0yxc0 2020 cord-275433-58unu79x 2007 The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. The class III PI3K vPS34 (also known as PIK3C3) generates phosphatidylinositol-3-phosphate (PtdIns3P) by phosphorylating The cellular events during digestion of self constituents or intracellular pathogens follow three distinct stages: initiation (formation of the phagophore), elongation (growth and closure) and maturation of a double membrane autophagosome into an autolysosome. In principle, autophagy may function in the direct elimination of viruses (as shown in vitro), in the breakdown of host factors required for viral replication or the inhibition of innate immune signalling, and in the promotion of cell survival either by maintaining bioenergetics in virally infected cells or by removing toxic self or viral components. In addition, numerous viruses inhibit the PKR (IFN-inducible doublestranded-RNA-dependent protein kinase) antiviral signalling pathway that is required for the induction of autophagy in virally infected cells or activate the autophagy-inhibitory class I PI3K-AKT-mTOR signalling pathway 63 . cord-275608-joyan7ij 2012 cord-277054-eq4obbte 2009 cord-279498-ez3yq7xi 2008 cord-279924-09uwhxs9 2014 cord-281691-3tl7f6tt 2008 cord-283035-tpqf458q 2009 cord-285091-2i2v5ecg 2012 showed that inhibitors of cysteine proteinases cystatin C and p41 form of major histocompatibility complex invariant chain did not inhibit cathepsin L and the authors suggested that cystatin F might be the inhibitor that selectively regulated cathepsin L activity in macrophages [69] . Gene targeting studies showed a critical role for the lysosomal cysteine protease cathepsin S in the late stages of Ii degradation in B cells, DCs and macrophages [89] [90] [91] and cathepsin L (V in humans) in thymic cortical epithelium [92] . An additional level of control is achieved by the proteolysis full length TLR7 and TLR9 by endosomal cysteine cathepsins and AEP.TLR9 can bind its ligand CpG DNA, but it cannot trigger activation signals without first being processed by endolysosomal proteases, which remove N-terminal region [98] [99] [100] [101] . The study shows that the functions of proteinases in the virus entry into the cell as well as in host immune response are relevant for the possible therapy with inhibitors. cord-289606-hypqpqs0 2016 cord-291070-y0wf456f 2005 PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED BALB/c is a computational system for the prediction of peptides binding to all five MHC molecules in BALB/c mice (H2 d ) class I (H2-K d , H2-L d and H2-D d ) and class II (I-A d and I-E d ) that allows analysis of proteins for the presence of binding motifs to all five H2 d molecules in parallel. We derived the initial quantitative matrices for PRED BALB/c using logarithmic equations based on the frequency of amino acids at specific positions within the training set of 9mer peptides as described previously (16) . To our knowledge, PRED BALB/c is the first online server for the prediction of peptides binding to a complete set of MHC molecules in a model organism (H2 d haplotype). cord-292596-ulu5y140 2020 cord-296347-fanlvxqs 2006 cord-298169-2133gahl 2020 Despite evidence of prominent immune implication in a significant subset of major psychiatric disorder patients such as schizophrenia, bipolar disorder or depression (Khandaker, Dantzer, Jones, 2017) or autism spectrum disorder (Meltzer & Van de Water, 2017) , deciphering the mechanistic link between the HLA system and these disorders was difficult, primarily because of the complex genetic architecture of the HLA system. This section reviews investigations of HLA gene candidate association in schizophrenia, bipolar disorders and Autism Spectrum Disorders, focusing on the risk/protection that HLA alleles/haplotypes may confer on specific sub-groups. Influenza and other infections prenatally can also increase risk of schizophrenia and autism spectrum disorders in the offspring, suggesting that HLA/MHC genetic variations may interact with prenatal infection in the etiology of major psychiatric disorders, although complicated by the immune-suppression that occurs in pregnancy (Shah et al, 2010) . cord-299786-wuve0tjz 2004 Dengue virus infection of immature myeloid dendritic cells has been shown to induce their maturation accompanied by the expression of major histocompatibility complex (MHC) class I and II antigens; the costimulatory molecules CD40, CD80, and CD86; and the dendritic cell marker CD83 (Libraty et al., 2001) . Flaviviruses, including dengue and West Nile (Shen et al., 1997) viruses, activate endothelial cell adhesion molecule expression by either direct (virus-mediated) or indirect (cytokine-mediated) mechanisms (see Section V,C). A major candidate event in such a route is the activation of endothelial cell adhesion molecules by a factor(s) (particularly TNF-) produced by dengue virus-infected blood monocytes . Thus the roles of prior immunity, antibody-enhanced virus infection, and immune-mediated pathologic effects on the vascular system are key points in understanding the pathogenesis of dengue hemorrhagic disease. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes cord-301293-jqy7lcbk 2006 cord-303069-ss6g3jkg 2020 A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. The aim of this study is to analyze envelope protein strains using in silico approaches looking for the conservancy, which is further studied to predict all potential epitopes that can be used after in vitro and in vivo confirmation as a therapeutic peptide vaccine [22, 23, 24] . Envelope protein from the SARS-CoV-2 was analyzed using the IEDB MHC-1 binding prediction tool to predict the T cell epitope suggested interacting with different types of MHC Class I alleles. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus cord-304635-z5vmhopa 2019 title: Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner However, based on the structures of a series of MHC I molecules, such as human HLA-B*2705 (Madden et al., 1991) , rhesus macaque Mamu-A*02 , and mouse H-2K d (Mitaksov and Fremont, 2006; Zhou et al., 2004) , there is a salt bridge positioned over the peptides formed by opposite charged residues from the α1 and α2 helices of MHC I, respectively. Herein, by determining the crystal structures of human MHC I HLA-B*4001 complexed with a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N)-derived T-cell epitope (Oh et al., 2011) and mouse MHC I H-2K d bound to an immunodominant T-cell epitope from human hepatitis B virus (HBV) core antigen (HBc) (Li et al., 2005) , we clearly demonstrated the molecular features of MHC I molecules with two different salt bridges formed by the residues pairs Arg62-Glu163 and Arg66-Glu163, respectively. cord-306096-2yl07bdq 2003 In the absence of viral infection, IDDM can be induced when such anergic CTL clones (of high or low affinity) in the periphery are activated as they pass into an islet environment where interferon-g or B7.1 are expressed [9, 10] . To examine whether molecular mimicry between a virus and a protein expressed in oligodendrocytes could lead to a central nervous system (CNS) autoimmune disease much like the demyelinating disease, multiple sclerosis, transgenic mice were generated whose oligodendrocytes expressed either the nucleoprotein or glycoprotein of a virus [41] . Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response Molecular mimicry in T-cell mediated autoimmunity: viral peptides activate human T-cell clones specific for myelin basic protein Oral insulin treatment suppresses virus-induced antigen-specific destruction of b cells and prevents autoimmune diabetes in transgenic mice cord-306308-zjq6cscm 2020 Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods. METHODS: Our analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes. CONCLUSIONS: Being aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2. cord-307445-r2os3kn9 2019 cord-308043-h0knm8y4 2009 These lines of evidence suggest a more elaborate TLR control of autophagy whereby TLR-adapter molecules interact with proteins from the autophagic pathway rather than by simply activating the classic hierarchical signaling cascades described heretofore. The authors demonstrated that the Atg5-Atg12 conjugate negatively regulates the antiviral immune response by interacting with the RIG-I-like receptor (s protein retinoic acid-inducible gene I (RIG-I) and IFN-␤ promoter stimulator 1 (IPS-1) thus, implying autophagy contributes to viral replication. In another study, the same group demonstrated that the fusion of influenza matrix protein 1 (MP1) with Atg8/LC3 drives this molecule to autophagosomes in different cell types and enhances recognition by antigen specific CD4+ T cells [117] . Accordingly, Atg6 silencing dampened this process, while rapamycin treatment enhanced priming of 85B-specific CD4 + T cells, strongly suggesting a role for autophagy in MHC class II presentation of antigens of bacterial origin. cord-310194-f5jtufja 2014 cord-310252-0cdqhrcw 2008 cord-310395-ae2x2wpg 2005 cord-310563-71940dh7 2019 cord-313138-y485ev30 2013 cord-319761-bu5pzbnv 2005 Accordingly, this review focuses on specific viral cell interactions that allow the virus to survive the cellular attack and evade the immune system, establish persistent infections, and cause chronic disease. 13, 14 Viruses regulate apoptosis by several mechanisms including the targeting of the tumor suppressor gene product p53, the Fas death receptor, and by producing caspase inhibitors and viral Bcl-2 homologs. 24, 25 The alpha herpesvirus HSV-1 encodes several antiapoptotic gene products (ie, ICP4, ICP27, c34.5, U s 3, gJ) [26] [27] [28] [29] [30] that modulate apoptosis at several levels, including antagonism of double-stranded RNA-activated protein kinase (PKR), a downstream induction molecule of the interferon signaling pathway 31, 32 Of note, all c-herpesviruses express viral homologues of cellular antiapoptotic genes, including 1 or 2 Bcl-2 homologues. In the majority of infections, viruses encode products that antagonize either the IFN signal transduction pathway or cellular proteins induced by IFN that are responsible for inhibiting virus replication (Fig 2) . cord-319993-er3sm4u8 2015 cord-322575-3goj00ej 2013 cord-329036-4bf8eiix 1994 cord-331555-yqhzyqs3 2003 title: Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. pulmonis infection as a model of chronic inflammation to determine the time course of changes in shape, number, and distribution of MHC class II expressing cells in the airway mucosa, with a focus on the region beneath the airway epithelium where M. In pathogen-free rats, a network of MHC class II expressing cells, identified by their OX6 immunoreactivity, occupied a thin layer just beneath the epithelium of the tracheal mucosa (Fig. 1A) . pulmonis infection resulted in conspicuous changes in the shape, number, and distribution of MHC class II expressing cells in the tracheal mucosa. cord-333309-21czobqy 2014 Interaction of lectin-type and other chaperones with ERAD substrates allows association with members of the protein disulfide isomerase (PDI) family, which generally are characterized by one or more thioredoxin-like motifs (CXXC; Brodsky and Skach, 2011) . In contrast to the rhomboid proteases, the Derlins lack proteolytic activity, suggesting that these proteins bind to ERAD substrates and target them to E3 ligases for ubiquitination and to p97 for membrane extraction (Brodsky, 2012) . These ubiquitin ligases are members of the cytosolic SCF (S-phase kinase-associated protein 1 (Skp1)-Cullin 1 (Cul1)-F-box) family, where the F-box components of the SCF complex recognize the N-glycans of the retrotranslocated substrate, e.g., Fbs1 and Fbs2 (Yoshida, 2007) . A proteasomal ATPase contributes to dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins cord-334592-54dofkxh 2011 Moreover, p62 is required for starvation and IFN-γ-induced targeting of Fau (and perhaps other ubiquitylated protein complexes) to mycobacteria-containing phagosomes, resulting in the generation of antimycobacterial Fau-derived peptides 42 .The role of p62 in innate immunity is probably evolutionarily ancient, as the Drosophila p62 orthologue REF(2)P was originally identified in a screen for modifiers of sigma virus replication 43 . The mechanisms by which autophagy genes mediate in vivo resistance to infection are not fully understood, but are likely to involve a combination of xenophagy, other autophagy-protein-dependent effects on microbial replication or survival, activation of innate and adaptive immune responses, and/or alterations in pathogen-induced cell death (Fig. 3 ). cord-334603-yt2pmxi3 2020 title: Mortality in COVID-19 disease patients: Correlating Association of Major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants Abstract As the 2019 (COVID-19) pandemic caused by the novel coronavirus, SARS-CoV-2 spreads globally, differences in adverse clinical management outcomes have been associated with associated with age >65years, male gender, and co-morbidities such as smoking, diabetes, hypertension, cardiovascular comorbidity and immunosuppression. HLA-DQB1*06:02 has been selected for increased resistance to Yersinia pestis in immigrants from Africa to Europe, engagement of CD4+ T-cells to HLA-DQB1*06:02 leads to increased, pro-inflammatory IL-17 production, independent of the MHC class II presented peptides (12) and confers increased risk to the development of anti-myelin directed autoimmune responses (13) . DRB3*02:02 is linked to Grave''s disease (44) , serum IgG antibodies to Chlamydia pneumoniae with essential hypertension (45) and acute necrotizing encephalopathy (46) In conclusion, there appears to be no selective pressure from MHC class I alleles for SARS-CoV-2 variants tested. cord-335342-u0ys2xcm 2007 11 The nature of the immune suppression may include secretion of immunosuppressive cytokines, 12 the expression of ligands (FAS-L) that initiate apoptosis in cytotoxic T-cells 13 and tumor variants that are deficient in antigen processing and presentation. As a consequence, specific cytotoxic T-cells generated by the vaccine protocol are unable to recognize and kill these tumor variants due to defective presentation of tumor associated antigen-derived peptides recognized by the CTLs. The MHC Class I restricted antigen presentation pathway consists of a number of genes encoded in the MHC Class I locus of human chromosome 6. [16] [17] [18] Conversely TAP1 expression has been associated with tumor infiltrating lymphocytes (TILs), a characteristic of good clinical outcome 8, 16, 19 and spontaneous regression of MAAs. 4 In our study, we examine the effect of the restoration of TAP1 expression on MHC Class I antigen surface expression in the murine MAA cell line, B16F10. cord-336343-qbcb9qi3 2020 cord-339091-3xk2w0d2 2010 The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. Initially, the pathogenic genome is scanned for "open reading frames" or ORFs. Once all ORFs have been identified, proteins are selected on the basis that they will be accessible to immune system surveillance, usually using some form of informatic-based prediction methodology or, more likely, set of methdologies. We shall below examine three key approaches: subcellular location prediction, sequence similarity, and empirical statistical approaches, typified by VaxiJen. For a protein to be accessible to surveillance by the immune system, it is often assumed to be physically external to the microbial organism or at least present on its surface rather than being sequestered away far from the roving eye of the immune system. cord-340781-z348xbn0 2019 Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 . cord-344105-9bw9rm6e 2020 After describing the recent sequencing technologies for immune receptor repertoires, we survey structural modeling methods for BCR and TCRs, along with methods for clustering such models. We review downstream analyses, including BCR and TCR epitope prediction, antibody-antigen docking and TCR-peptide-MHC Modeling. The Immcantation framework [18, 19] and TRUST (TCR repertoire utilities for solid tissue) [20] can be also used for the same purpose among many other available tools not covered here Though single chain information alone is usually not enough to explain the binding of the receptor to the target epitope, there are several methods applicable to bulk sequencing data. Based on the observation that there are specific positions in TCR CDR3 regions that contact antigen peptides and that the presence of particular sequence motifs can define TCR clusters, Glanville et al., developed the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm [63, 64] . cord-346032-188gnf8j 2007 cord-347039-eap592i7 2003 Receptors are recognized as important determinants of virus host range and tissue tropism; and some host resistance/susceptibility loci encode molecules that are expressed on the cell surface. Another example of natural host resistance is the restriction of ecotropic Murine LEUKEMIA VIRUS (MuLV) infection by the mouse Fv4 gene. The effort to understand the genetic basis of susceptibility to viral disease is driven by three considerations: (1) the increased public awareness of the toll imposed by viruses on the host; (2) the increase in susceptible human populations because of longer life expectancy, frequently accompanied by chronic illness, and the consequences of advances in medical technology, including immunosuppressive therapies for organ transplantation or treatment of malignancy; and (3) the need to develop new therapies for infections caused by multidrug-resistant Human killer-cell immunoglobulin-type receptor (KIR) is considered to be a functional homolog of mouse Ly49. Mouse genetics has also demonstrated that recognition and destruction of virus-infected cells by NK cells is mediated by specific interactions between activating NKcell receptors and viral target molecules. cord-347298-7kqrl3rv 2010 cord-349225-504kr50e 2000 cord-350083-kldu8q8x 2015 title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach cord-350583-0t1kly3i 2016 cord-350772-fp5d9if0 2008 cord-352150-ey9kc7zj 2016 cord-353877-wzndpcq3 2020 cord-354030-8tfg881h 2020 cord-355075-ieb35upi 2012 alecto transcriptome provides information on a variety of immune genes not previously identified in any bat species and represents an important starting point for examining the antiviral activity of these molecules. To enrich for sequences corresponding to cytokines and innate immune genes, the second dataset was derived from pooled total RNA obtained from mitogen-stimulated spleen, white blood cells and lymph node and unstimulated thymus and bone marrow obtained from one pregnant female and one adult male flying fox. A full length transcript, encoding a 667 amino acid protein was identified in our bat transcriptome datasets and found to be orthologous to Mx1 based on comparison with known mammalian Mx1 and Mx2 family members (Figure 4a and data not shown). Genes involved in the adaptive immune system, including MHC class I and II genes and T and B cell receptors and co-receptors were highly represented in both the thymus and pooled datasets providing evidence that bats have all of the components necessary to mount an adaptive immune response.