Paired lines of C3H mouse fibroblasts transformed with murine sarcoma virus (Kirsten strain) were prepared that express high or low levels ofclass II major histocompatibility complex antigen after treatment with interferon y (IFN-y) . Here, we described a comparison of the tumorigenicity of these lines in euthymic syngeneic and thymus-deficient nu/nu mice and in mice depleted of IFN-y . The class II-inducible cells are clearly less tumorigenic than the noninducible cells in syngeneic mice, but of similar tumorigenicity in nu/nu mice and in mice treated with antibodies to deplete IFN-y . We propose that in this system, IFN-y induction of class II antigens on the tumor cell surface operates to limit tumor growth ; ras expression, which inhibits induction of class II antigens, prevents this and so allows tumor growth .
We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #type:clinical-trial,attrs:text:NCT00085930″,term_id:NCT00085930″NCT00085930. Introduction Adoptively transferred T cells Rabbit Polyclonal to ZADH2 can recognize tumor-associated antigens presented in association with MHC molecules on the cell surface. However, many cancer cells and solid tumors have defects in antigen processing and presentation,1,2 including down-regulation of and/or failure to express MHC molecules.3,4 Introducing tumor-specific chimeric antigen receptors (CARs) into adoptively transferred T cells allows them to recognize tumor-associated antigens in an Resminostat hydrochloride manufacture MHC-independent manner while retaining their ...
Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other
TY - JOUR. T1 - Bacterial and Host Factors Involved in the Major Histocompatibility Complex Class Ib-Restricted Presentation of Salmonella Hsp 60. T2 - Novel Pathway. AU - Lo, Wei Feng. AU - Dunn, Cory D.. AU - Ong, Helena. AU - Metcalf, Eleanor S.. AU - Soloski, Mark J.. PY - 2004/5/1. Y1 - 2004/5/1. N2 - Previously, a peptide epitope derived from the Hsp 60 molecule of Salmonella that is presented by the major histocompatibility complex (MHC) class Ib molecule Qa-1 to CD8+ cytotoxic T cells (CTLs) was described. In the present study we investigated the Salmonella-induced processing and presentation pathway for generating this Qa-1-restricted epitope. Live bacteria and, to a lesser extent, opsonized heat-killed bacteria are able to sensitize target cells for lysis by Salmonella-specific CTL. In contrast, heat-killed bacteria cannot sensitize target cells. Presentation of the Hsp 60 epitope appears independent of bacterial internalization, because cytochalasin D does not affect presentation. ...
TY - JOUR. T1 - Association of LMP2 and LMP7 genes within the major histocompatibility complex with insulin-dependent diabetes mellitus. T2 - Population and family studies. AU - Deng, G. Y.. AU - Muir, A.. AU - Maclaren, N. K.. AU - She, J. X.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - LMP2 and LMP7, two subunits of the proteasomes encoded in the major histocompatibility complex, are speculated to play a role in the generation of endogenous peptides for presentation by class I molecules to cytotoxic T cells. Their possible role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) has not been documented. In this study of Caucasian subjects, we have analyzed the polymorphisms of four genes within the HLA class II region (LMP2, LMP7, and HLA-DRB1 and -DQB1) in 198 unrelated IDDM patients and 192 normal controls ascertained from the southeastern United States. A genomic polymorphism of LMP7 was found strongly associated with IDDM, and the Arg/His-60 polymorphism in LMP2 was found associated ...
Understanding the structure and variability of adaptive loci such as the major histocompatibility complex (MHC) genes is a primary research goal for evolutionary and conservation genetics. Typically, classical MHC genes show high polymorphism and are under strong balancing selection, as their products trigger the adaptive immune response in vertebrates. Here, we assess the allelic diversity and patterns of selection for MHC class I and class II loci in a threatened shorebird with highly flexible mating and parental care behaviour, the Snowy Plover (Charadrius nivosus) across its broad geographic range. We determined the allelic and nucleotide diversity for MHC class I and class II genes using samples of 250 individuals from eight breeding population of Snowy Plovers. We found 40 alleles at MHC class I and six alleles at MHC class II, with individuals carrying two to seven different alleles (mean 3.70) at MHC class I and up to two alleles (mean 1.45) at MHC class II. Diversity was higher in the peptide
Celiac disease, also known as celiac sprue, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac ...
The results presented here add a critical lineage to the emerging picture of MHC evolution in amniotes, with a genome-level characterization of MHC organization in an evolutionarily divergent reptile, the tuatara. The tuatara MHC region appears to be large with a high repeat content. We found a total of seven class I sequences and 11 class II β sequences, but some appeared to represent pseudogenes. Chromosome 13q appears to contain the core MHC, as clones containing classical class I, class II beta, and class II alpha chain genes map to here, but additional class I genes were located chromosome 4p.. The MHC in tuatara has low gene density compared with other species. We found at most five genes on individual BAC clones, and many clones contained only one or two genes and a high number of repetitive elements. The low density of tuatara MHC genes is a likely reason for challenges in identifying other MHC-associated genes like TAP1, TAP2, TAPBP, or C4 or framework genes like DAXX, BRD2, or TNXB on ...
TY - JOUR. T1 - T cell homeostasis in tolerance and immunity. AU - Marleau, Annette M.. AU - Sarvetnick, Nora. PY - 2005/9. Y1 - 2005/9. N2 - The size of the peripheral T cell pool is remarkably stable throughout life, reflecting precise regulation of cellular survival, proliferation, and apoptosis. Homeostatic proliferation refers to the process by which T cells spontaneously proliferate in a lymphopenic host. The critical signals driving this expansion are space, contact with self-major histocompatibility complex (MHC)/peptide complexes, and cytokine stimulation. A number of studies have delineated an association between T cell lymphopenia, compensatory homeostatic expansion, and the development of diverse autoimmune syndromes. In the nonobese diabetic mouse model of type 1 diabetes, lymphopenia-induced homeostatic expansion fuels the generation of islet-specific T cells. Excess interleukin-21 facilitates T cell cycling but limited survival, resulting in recurrent stimulation of T cells ...
In several species, including rodents and fish, it has been shown that the Major Histocompatibility Complex (MHC) influences mating preferences and, in some cases, that this may be mediated by preferences based on body odour. In humans, the picture has been less clear. Several studies have reported a tendency for humans to prefer MHC-dissimilar mates, a sexual selection that would favour the production of MHC-heterozygous offspring, who would be more resistant to pathogens, but these results are unsupported by other studies. Here, we report analyses of genome-wide genotype data (from the HapMap II dataset) and HLA types in African and European American couples to test whether humans tend to choose MHC-dissimilar mates. In order to distinguish MHC-specific effects from genome-wide effects, the pattern of similarity in the MHC region is compared to the pattern in the rest of the genome. African spouses show no significant pattern of similarity/dissimilarity across the MHC region (relatedness ...
Viruses encounter changing selective pressures during transmission between hosts, including host-specific immune responses and potentially varying functional demands on specific proteins. The human immunodeficiency virus type 1 Nef protein performs several functions potentially important for successful infection, including immune escape via down-regulation of class I major histocompatibility complex (MHC-I) and direct enhancement of viral infectivity and replication. Nef is also a major target of the host cytotoxic T-lymphocyte (CTL) response. To examine the impact of changing selective pressures on Nef functions following sexual transmission, we analyzed genetic and functional changes in nef clones from six transmission events. Phylogenetic analyses indicated that the diversity of nef was similar in both sources and acutely infected recipients, the patterns of selection across transmission were variable, and regions of Nef associated with distinct functions evolved similarly in sources and ...
Antigen presentation requires intracellular processing of native antigens to produce immunogenic peptides that bind to major histocompatibility complex class II (MHC-II) molecules. In functional studies of antigen processing by elicited peritoneal macrophages, MHC-II-peptide complexes were formed intracellularly. Immunogenic peptides were not released to bind surface MHC-II molecules. Ultrastructural studies employing immunogold staining in ultrathin cryosections of these macrophages showed large amounts of MHC-II molecules in intracellular sac-like vacuoles in the peripheral cytoplasm; most of these were negative for the lamp 1 lysosomal/endosomal membrane protein and cathepsin D. MHC-II molecules were also present in endosomes containing cathepsin D and lamp 1 as well as previously internalized gold-transferrin. The intracellular pool of MHC-II molecules was only slightly decreased by treatment with cycloheximide for 3 hr, indicating that it consisted mainly of endocytosed, recycling molecules, as
Background: The major histocompatibility complex (MHC) is responsible for presenting antigens (epitopes) on the surface of antigen-presenting cells (APCs). When pathogen-derived epitopes are presented by MHC class II on an APC surface, T cells may be able to trigger an specific immune response. Prediction of MHC-II epitopes is particularly challenging because the open binding cleft of the MHC-II molecule allows epitopes to bind beyond the peptide binding groove; therefore, the molecule is capable of accommodating peptides of variable length. Among the methods proposed to predict MHC-II epitopes, artificial neural networks (ANNs) and support vector machines (SVMs) are the most effective methods. We propose a novel classification algorithm to predict MHC-II called sparse representation via 1-minimization. Results: We obtained a collection of experimentally confirmed MHC-II epitopes from the Immune Epitope Database and Analysis Resource (IEDB) and applied our 1-minimization algorithm. To benchmark the
RefSeq Summary (NM_021160): A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010 ...
Spliceosome RNA helicase BAT1 is an enzyme that in humans is encoded by the BAT1 gene. This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and also plays an important role in mRNA export from the nucleus to the cytoplasm. A cluster of genes, BAT1-BAT5, is localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants encoding the same protein have been described. ENSG00000225073, ENSG00000237889, ENSG00000229496, ENSG00000215425, ENSG00000235439, ENSG00000225859, ENSG00000230624 GRCh38: Ensembl release 89: ENSG00000198563, ENSG00000225073, ENSG00000237889, ENSG00000229496, ENSG00000215425, ...
We investigated the role of the complementarity determining region 1 (CDR1) of T cell receptor (TCR) beta chain both in antigen/major histocompatibility complex I (MHC I) and in superantigen (SAg)/MHC II complex recognition. Residues 26 to 31 of the V beta 10 domain of a TCR derived from an H-2Kd-restricted cytotoxic clone were individually changed to alanine, using site-directed mutagenesis, and the mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha-beta-T hydridoma. These mutations affected antigen/H-2Kd complex recognition, although to a different extent, as estimated by interleukin 2 production. Certain mutations also affected differently the recognition of two Staphylococcal toxins, exfoliative toxin and Staphylococcal enterotoxin C2, presented by HLA-DR1. Whereas mutation of residues D30 or T31 affect the recognition of both toxins, residues T26, L27, and H29 are critical for the recognition of only one of the SAgs. These observations ...
Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.[5][6][7] This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants.[7] ...
Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that ...
Scientists at Fred Hutchinson Cancer Research Center have developed a new method for analyzing the Major Histocompatibility Complex (MHC) of the human genome. This large region, found on chromosome 6, encodes more than 400 known genes. The best known of these genes are the HLA genes that govern tissue type and participate in the immune system by protecting people from infection or by governing susceptibility to autoimmune diseases or cancer. The method may have the potential of being an efficient way to map genes in the MHC that are responsible for many human diseases, and might also be useful in studying other gene complexes that have a lot of variability ...
Enhanced MHC class I expression is a prominent early feature of pancreatic islets in autoimmune diabetes and islet transplantation. However, the nature of class I MHC loci potentially critical to the onset and progression of insulitis in humans remains poorly defined. Our findings reveal a previously unrecognized complexity of islet immunogenicity, to include MHC determinants such as HLA-G with specialized immunoregulatory functions. Indeed, the long-lasting, self-contained, peri-islet and periductal lymphoid infiltrates, hallmark of the early stages of autoimmune diabetes and the evidence for T- and NK cell-dependent regulatory networks in those lymphoid infiltrates (24,25), indicate that destructive processes are counterbalanced by immunoregulatory mechanisms at sites of islet immunity. Our observation that pancreatic islets and ducts express HLA-G constitutively and upregulate this MHC determinant in response to proinflammatory cytokines raises the possibility that mechanisms of immune ...
Genetic compatibility refers to how well the genes of two parents function together in their offspring. Choosing genetically compatible mates could result in optimally fit offspring and notably affect reproductive fitness. However, the genetic compatibility model is limited to specific traits due to complex genetic interactions (e.g. major histocompatibility complex in humans and mice). The choosy sex must know their own genotype as well as the genotypes of potential mates in order to select the appropriate partner.[35] This makes testing components of genetic compatibility difficult and controversial. A controversial but well-known experiment suggests that human females use body odor as an indicator of genetic compatibility. In this study, males were given a plain T-shirt to sleep in for two nights in order to provide a scent sample. College women were then asked to rate odors from several men, some with similar MHC (major histocompatibility complex) genes to their own and others with ...
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Gentaurs MHCE/HLA-E CLIA kit utilizes the Sandwich- CLIA principle. The micro CLIA plate provided in this kit has been pre-coated with an antibody specific to Human MHCE/HLA-E . Standards or samples are added to the micro CLIA plate wells and ...
TY - JOUR. T1 - Prolonged survival of mice with glioma injected intracerebrally with double cytokine-secreting cells. AU - Lichtor, T.. AU - Glick, R. P.. AU - Kim, Tae Sung. AU - Hand, R.. AU - Cohen, E. P.. PY - 1995/12/1. Y1 - 1995/12/1. N2 - A novel approach toward the treatment of glioma was developed in a murine model. The genes for both interleukin-2 (IL-2) and interferon-γ (IFN-γ) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determinants (H-2(k)). The double cytokine-secreting cells were then cotransplanted intracerebrally with the G1261 murine glioma cell line into syngeneic C57BL/6 mice (H-2b) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice with glioma injected with the cytokine-secreting allogeneic cells was significantly prolonged, relative to the survival of mice receiving equivalent numbers of glioma cells alone. Using a standard 51Cr-release ...
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1OSZ: Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands.
2P5E: Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry
The dbMHC database provides an open, publicly accessible platform for DNA and clinical data related to the human Major Histocompatibility Complex (MHC). The dbMHC provides access to human leukocyte antigen (HLA) sequences, HLA allele and haplotype frequencies, and clinical datasets ...
Purified recombinant protein of Human major histocompatibility complex, class II, DR beta 5 (HLA-DRB5), full length, with N-terminal GST and C-terminal His tag, expressed in E. coli, 50ug
The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different h …
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pCMV-SPORT6-CDKN1B-G326T plasmid,pCMV-SPORT6-CDKN1B-G326T,pCMV-SPORT6-CDKN1B-G326T plasmid,pCMV-SPORT6-CDKN1B-G326T sequence,pCMV-SPORT6-CDKN1B-G326T map
2oje: Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen.
The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped t …
Classical alphabeta T cells protect the host by monitoring intracellular and extracellular proteins in a two-step process. The first step is protein degradation and combination with a major histocompatibility complex (MHC) molecule, leading to surface expression of this amalgam (antigen processing). The second step is the interaction of the T cell receptor with the MHC-peptide complex, leading to signaling in the T cells (antigen recognition). The context for this interaction is a T cell-antigen presenting cell junction, known as an immunological synapse if symmetric and stable and as a kinapse if asymmetric and mobile. The physiological recognition of a ligand takes place most efficiently in the F-actin-rich lamellipodium and is F-actin dependent in stages of formation and triggering and myosin II dependent for signal amplification. This review discusses how these concepts emerged from early studies on adhesion, signaling, and cell biology of T cells.
To pursue our first goal, we have focused on developing advanced imaging techniques to understand the molecular interactions that underlie the process by which a particular T cell recognizes fragments of an antigen (peptide) that are bound to molecules of the major histocompatibility complex (MHC) and displayed on the surfaces of cells. These peptide-MHC complexes are then recognized by the T cell antigen receptor (TCR), an antibody-like molecule present on most T cells. The TCR is closely associated with the CD3 polypeptides, which mediate intracellular signaling through a kinase cascade. Our previous work and that of others characterized the biochemistry and genetics of TCRs, but in recent years we have focused on how these molecules operate in the larger context of T cell recognition, a context that includes other molecules on the T cell surface that work with the TCR, and on how ligand binding triggers T cell activation. Video microscopy and other advanced imaging techniques, such as ...
Yin L, Huseby E, Scott-Browne J, Rubtsova K, Pinilla C, Crawford F, Marrack P, Dai S, Kappler JW. A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers. Immunity. 2011 Jul 22; 35(1):23-33 ...
CD4, 0.1 ml. This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a receptor for the human immunodeficiency virus.
Description: The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]). NCBI Entrez Gene , GeneCards , Harmonizome ...
The discovery of CD25 as a marker of Tregs raised a concern that Tregs may not represent a distinct T-cell lineage, but a particular state of activation, because CD25 is upregulated by all activated T cells. Other highly expressed markers on CD25+ Tregs, including CTLA-4 and GITR, are also upregulated upon activation of T cells. However, adoptive transfer of CD4+CD25+ T cells into lymphopenic mice showed that they proliferate in an MHC-dependent manner and, despite a decline in CD25 expression, their suppressive capacity increases (7). This finding and others spurred an intense exploration of potential genetic mechanisms underlying the differentiation and function of Tregs and a search for a more specific marker of these cells.. These efforts resulted in identification of Foxp3, an X chromosome-encoded member of the forkhead transcription factor family, as a specific marker of Tregs (8-10). Foxp3 was identified as the gene whose loss-of-function mutation is responsible for a disease in mutant ...
Clone REA642 recognizes the mouse V beta 2 T cell receptor (TCR Vβ2). The T cell receptor is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. It is a disulfide-linked membrane-anchored heterodimeric glycoprotein normally consisting of the highly variable alpha and beta chains expressed as part of a complex with the invariant CD3 chain molecules. The α and β TCR chains are composed of constant and variable regions, each encoded by distinct gene segments. Additional information: Clone REA642 displays negligible binding to Fc receptors. - Great Britain
Clone REA559 recognizes the human Vβ11 T cell receptor (TCR Vβ11). The TCR is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. It is a disulfide-linked membrane-anchored heterodimeric glycoprotein normally consisting of the highly variable α and β chains expressed as part of a complex with the invariant CD3 chain molecules. TCR Vβ11 is expressed on a subset of α/β T cells. Additional information: Clone REA559 displays negligible binding to Fc receptors. - Lëtzebuerg
HLA-DQ DQ1 binding pocket with ligand major histocompatibility complex, class II, DQ Structure Type Cell surface receptor Quartenary αβ-heterodimer, ligand
The invention concerns a molecule of pharmaceutical interest, preferably a major histocompatibility complex (MHC) ligand, comprising a glutamic acid or a glutamine at its N-terminal, in the form of a physiologically acceptable addition salt, and a vaccine comprising such a ligand.
HLA-A2 antibody [BB7.2] (major histocompatibility complex, class I, A) for FACS, IHC-Fr, IP. Anti-HLA-A2 mAb (GTX75803) is tested in Human samples. 100% Ab-Assurance.
HLA-A antibody (major histocompatibility complex, class I, A) for ICC/IF, IHC-P, WB. Anti-HLA-A pAb (GTX54099) is tested in Human, Mouse samples. 100% Ab-Assurance.
Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and-negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G ...
Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and-negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G ...
The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of |44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122
Gentaur molecular products has all kinds of products like :search , EIAab \ ELISA kit Class I histocompatibility antigen-like protein,Major histocompatibility complex class I-related gene protein,MHC class I-related gene protein,Mouse,Mr1,Mr1a,Mus musculus \ E0910m for more molecular products just contact us
To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side ...
TY - JOUR. T1 - High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I: implications for T-Cell receptor engagement and T-cell immunodominance. AU - Tynan, Fleur Elizabeth. AU - Borg, Natalie. AU - Miles, John J. AU - Beddoe, Travis Clarke. AU - Elhassen, Diah. AU - Silins, Sharon L. AU - van Zuylen, Wendy JM. AU - Purcell, Anthony W. AU - Kjer-Nielsen, Lars. AU - McCluskey, James. AU - Burrows, S R. AU - Rossjohn, Jamie. PY - 2005. Y1 - 2005. U2 - 10.1074/jbc.M503060200. DO - 10.1074/jbc.M503060200. M3 - Article. VL - 280. SP - 23900. EP - 23909. JO - Journal of Biological Chemistry. JF - Journal of Biological Chemistry. SN - 1083-351X. IS - 25. ER - ...
Yilla, M.; Hickman, C.; McGrew, M.; Meade, E.; Bellini, W.J., 2003: Edmonston measles virus prevents increased cell surface expression of peptide-loaded major histocompatibility complex class II proteins in human peripheral monocytes
The major histocompatibility complex (MHC) is a collection of genes coding for MHC molecules found on the surface of all nucleated cells of the body. In humans, the MHC genes are also referred to as human leukocyte antigen (HLA) genes. Mature red blood cells, which lack a nucleus, are the only cells that do not express MHC molecules on their surface.. There are two classes of MHC molecules involved in adaptive immunity, MHC I and MHC II (Figure 14.11). MHC I molecules are found on all nucleated cells; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity. In contrast, MHC II molecules are only found on macrophages, dendritic cells, and B cells; they present abnormal or nonself pathogen antigens for the initial activation of T cells.. Both types of MHC molecules are transmembrane glycoproteins that assemble as dimers in the cytoplasmic membrane of cells, but their structures are quite different. MHC I molecules are ...
TY - JOUR. T1 - Analysis of T-cell hybridomas with an unusual MHC class II-dependent ligand specificity. AU - Mendiratta, S. K.. AU - Singh, Nagendra. AU - Bal, V.. AU - Rath, S.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - We have characterized two unusual T-cell hybridomas, 1E3 and 3B8, from H-2(k) mice immunized with I-Ab-transfected L cells (H-2(k)), that are stimulated by L cells transfected with I-Ab, I-A(k) or I-Eb, but not by non-transfected L cells. These hybridomas could not be stimulated by spleen cells from H-2(i3), H-2(k), H-2b or H-2(d) mice. Monoclonal anti-I-A antibodies did not block their responses, suggesting that mouse major histocompatibility complex (MHC) class II molecules may be peptide donors rather than restriction elements for them. The stimulation of these hybridomas by fibroblast targets was not blocked by an anti-H-2k(k),D(k)-specific monoclonal antibody. Lipopolysaccharide (LPS)-activated splenic and peritoneal exudate cells from H-2(k), H-2(d), H-2(i3), H-2b as well as ...
Sequence variation at a major histocompatibility complex (MHC) class II gene was examined in Hypogeomys antimena, a monogamous endemic rodent of Madagascar. The study was conducted throughout its remaining geographical range (20 × 40 km) by direct sequencing and single-strand conformation polymorphism (SSCP). The objectives of the study were: (i) to investigate levels of polymorphism in the MHC complex of a highly endangered species that experienced a severe reduction in population size; and (ii) to investigate the genetic mating system by assessing the frequency of extra-pair paternity (EPP) as EPP might have important consequences to increase gene flow and, therefore, genetic variability within a population. The amplified gene segment had a very low variability (only two alleles) in H. antimena compared with other mammalian species. The alleles segregated consistently with Mendelian expectations in families. No case of EPP was found. The present data suggest no difference between the social ...
The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establishing a new upper limit for the solution affinity at 2.5 mM. However, when presented multivalently on magnetic beads, soluble CD4 bound pMHC II-expressing B cells, confirming that it is active and allowing mapping of the native coreceptor binding site on pMHC II. Whereas binding was undetectable in solution, the affinity of the CD4/pMHC II interaction could be measured in 2D using CD4- and adhesion molecule-functionalized, supported lipid bilayers, yielding a 2D Kd of ∼5,000 molecules/μm(2) This value is two to three orders of magnitude higher than previously measured 2D Kd values for interacting
Kennedy, L J and Quarmby, S and Happ, G M and Barnes, A and Ramsey, I K and Dixon, R M and Catchpole, B and Rusbridge, C and Graham, P A and Hillbertz, N S and Roethel, C and Dodds, W J and Carmichael, N G and Ollier, W E R (2006) Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele. TISSUE ANTIGENS, 68 (1). pp. 82-86. Full text not available from this repository ...
Aguilar A and Garza JC (2007). Patterns of historical balancing selection on the salmonid major histocompatibility complex class II beta gene. J. Mol. Evol. 65: 34-43. http://dx.doi.org/10.1007/s00239-006-0222-8 PMid:17593422 Apanius V, Penn D, Slev PR, Ruff LR, et al. (1997). The nature of selection on the major histocompatibility complex. Crit. Rev. Immunol. 17: 179-224. http://dx.doi.org/10.1615/CritRevImmunol.v17.i2.40 PMid:9094452 Archie EA, Henry T, Maldonado JE, Moss CJ, et al. (2010). Major histocompatibility complex variation and evolution at a single, expressed DQA locus in two genera of elephants. Immunogenetics 62: 85-100. http://dx.doi.org/10.1007/s00251-009-0413-8 PMid:20058003 Axtner J and Sommer S (2007). Gene duplication, allelic diversity, selection processes and adaptive value of MHC class II DRB genes of the bank vole, Clethrionomys glareolus. Immunogenetics 59: 417-426. http://dx.doi.org/10.1007/s00251-007-0205-y PMid:17351770 Baker CS, Vant MD, Dalebout ML, Lento GM, et al. ...
Project Description. Molecular methods are powerful approches for the study of natural selection, and several of DeWoodys students at Purdue have studied natural selection. One, Sara Turner, raised Atlantic salmon and compared levels of relatedness in the parents to determine if outbred parents have greater hatching success than closely related parents. She also looked at MHC variability and its potential impact on survivorship in light of evidence that Atlantic salmon choose their mates on the basis of MHC genotype. Sara found that MHC zygosity influences susceptibility to bacterial kidney disease, and that MHC genotype has little influence on early embryo survivorship.. Another student, Nick Marra, used RNA-seq to characterize the kangaroo rat transcriptome in an effort to identify genes involved in a) immunobiology and b) osmoregulation. Nick found signatures of selection on key genes families, including solute carrier proteins (SLCs).. Finally, Yanzhu (aka Bamboo) Ji studied how ...
Class I major histocompatibility complex (MHCI) is known to modulate activity-dependent synaptic remodeling in the visual system and to regulate synaptic plasticity in the hippocampus. Here, the authors show that MHCI negatively regulates the density and function of cortical synapses during their initial establishment. Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in β2m−/− mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of
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Research Interest. Regulation of graft rejection by direct and indirect alloreactivity pathways Solid organ transplantation remains the treatment of choice for numerous patients with kidney, heart, and lung diseases. The recognition of allogeneic major histocompatibility complex antigens by T lymphocytes, a phenomenon called alloreactivity, is essential to initiate the immune responses responsible for graft rejection during organ transplants and it remains a major hindrance to the success of transplantation. In spite of the progress made in the recent years on the description of T cell recognition, the molecular basis of alloreactivity remains elusive. Moreover, little is known about the actual contribution of allorecognition to the physiology of graft rejection in vivo. Two pathways of alloreactivity have been described. Indirect alloreactivity corresponds to the classical pathway of antigen presentation, as the allogeneic MHC molecules are degraded and the peptides derived from these molecules ...
Bompeixe EP, Santos PSC, Vargas RG, Linsingen R, Zeck SC, Wowk PF, Bicalho MG (2013). HLA class II polymorphisms and recurrent spontaneous abortion in a Southern Brazilian cohort. International Journal of Immunogenetics. 40(3):186-91. Santos PSC, Courtiol A, Heidel A, Höner O, Heckmann I, Nagy M, Mayer F, Platzer M, Voigt CC, Sommer S (2016). MHC-dependent mate choice is linked to a trace-amine-associated receptor gene in a mammal. Scientific Reports 6, 38490. Santos PSC, Michler F-U, Sommer S (2017) Can MHC-assortative partner choice promote offspring diversity? A new combination of MHC-dependent behaviors among sexes in a highly successful invasive mammal. Molecular Ecology, in press (20.01.2017).. ...
UPDATE: In April 2010, the WHO Nomenclature Committee for Factors of the HLA System introduced a modification of the nomenclature outlined in the manual; the new nomenclature introduces delimiters in the form of colons, which removes the restriction of only allowing 99 alleles in 1 group. Hence the former HLA-DQB1*0503 is now expressed as HLA-DQB1*05:03 (Tait BD. The ever-expanding list of HLA alleles: changing HLA nomenclature and its relevance to clinical transplantation. Transplant Rev [Orlando]. 2011;25[1]:1 8.). This change was made March 29, 2011. [I]n transplantation, Histocompatibility Leads to Acceptance; in anthropology, Human populations are Located by Allelic variation; in
Because most immunocompetent individuals do not suffer from CMV disease during either primary or recurrent infections, the immune system must be effective in controlling replication. However, this simplistic assumption masks a level of complexity between the virus and host that is still being unravelled. The B cell response to CMV is largely dominated by an anti-glycoprotein B cell response, and most of the neutralising antibodies are also directed against this protein.14, 15 In contrast, the cytotoxic T cell (CD8) response is almost exclusively directed against the pp65 (UL83) protein and epitopes have been mapped for human major histocompatibility complex (HLA) types A*0201, B*0701, B*0801, and B*3501 (table 1).16, 17 The frequency of cytotoxic T lymphocytes (CTLs) against CMV in immunocompetent individuals has been estimated to be 1/5000 by classic endpoint dilution chromium release assays but, using more recently developed HLA class I tetramer technology, this frequency may be much ...
IMMUNREAKTION + IMMUNANTWORT (IMMUNOLOGIE); DENDRITISCHE ZELLEN (IMMUNOLOGIE); MHC-KLASSE-II-MOLEKÜLE (IMMUNOLOGIE); ZENTRALNERVENSYSTEM (NEUROLOGIE); IMMUNE REACTION + IMMUNE RESPONSE (IMMUNOLOGY); DENDRITIC CELLS (IMMUNOLOGY); MHC CLASS II MOLECULES (IMMUNOLOGY); CENTRAL NERVOUS SYSTEM (NEUROLOGY ...
The native Hawaiian honeycreepers represent a classic example of adaptive radiation and speciation, but currently face one the highest extinction rates in the world. Although multiple factors have likely influenced the fate of Hawaiian birds, the relatively recent introduction of avian malaria is thought to be a major factor limiting honeycreeper distribution and abundance. We have initiated genetic analyses of class II β chain Mhc genes in four species of honeycreepers using methods that eliminate the possibility of sequencing mosaic variants formed by cloning heteroduplexed polymerase chain reaction products. Phylogenetic analyses group the honeycreeper Mhc sequences into two distinct clusters. Variation within one cluster is high, with dN , dS and levels of diversity similar to other studies of Mhc (B system) genes in birds. The second cluster is nearly invariant and includes sequences from honeycreepers (Fringillidae), a sparrow (Emberizidae) and a blackbird (Emberizidae). This highly ...
Once in contact with the host immune system, the microorganism faces the hosts tightly integrated cellular and humoral immune responses. Cellular immunity, comprising T lymphocytes, macrophages, and natural killer cells, primarily recognizes and combats pathogens that proliferate intracellularly. Cellular immune mechanisms are important in immunity to all classes of infectious agents, including most viruses and many bacteria (e.g., Mycoplasma, Chlamydophila, Listeria, Salmonella, and Mycobacterium), parasites (e.g., Trypanosoma, Toxoplasma, and Leishmania), and fungi (e.g., Histoplasma, Cryptococcus, and Coccidioides). Usually, T lymphocytes are activated by macrophages and B lymphocytes, which present foreign antigens along with the hosts own major histocompatibility complex antigen to the T-cell receptor. Activated T cells may then act in several ways to fight infection. Cytotoxic T cells may directly attack and lyse host cells that express foreign antigens. Helper T cells stimulate the ...
HLA - HLA (Myc-DDK-tagged)-Human major histocompatibility complex, class I, B (HLA-B) available for purchase from OriGene - Your Gene Company.
Background: Dendritic cells (DCs) are professional antigen-presenting cells able to induce immunity or tolerance. The interactions of immature DCs with naive T lymphocytes induce peripheral tolerance through mechanisms that include anergy or deletion of lymphocytes or the generation of regulatory T cells. Because of the central role of DCs in the immune response, they are potential targets for the induction of experimental tolerance. Thus, the generation of immature (tolerogenic) DCs able to capture and present alloantigens to T cells represents an important aim in our efforts to achieve better transplant acceptance. Methods: In this work, we generated immature DCs by using vitamin D 3 (VD3) during the process of DC differentiation. Results: The VD3DCs showed an immature phenotype characterized by a low expression of major histocompatibility complex antigens of class II, CD86, and CD80 molecules and the secretion of a tolerogenic cytokine pattern. Furthermore, we showed that VD3DCs ...
TY - JOUR. T1 - Protein Nanoparticle Formation Using a Circularly Permuted α-Helix-Rich Trimeric Protein. AU - Kawakami, Norifumi. AU - Kondo, Hiroki. AU - Muramatsu, Masayuki. AU - Miyamoto, Kenji. PY - 2017/2/15. Y1 - 2017/2/15. N2 - We here report the production of highly spherical protein nanoparticles based on the domain-swapping oligomerization of a circularly permuted trimeric protein, major histocompatibility complex (MHC) class II associated chaperonin. The size distribution of the nanoparticles can be adjusted to between 40 and 100 nm in diameter, and thus, these particles are suitable as drug carriers following purification under basic conditions. Our approach involves no harsh treatments and could provide an alternative approach for protein nanoparticle formation.. AB - We here report the production of highly spherical protein nanoparticles based on the domain-swapping oligomerization of a circularly permuted trimeric protein, major histocompatibility complex (MHC) class II ...
Instruction Dr. Lamont instructs courses in genetic regulation of livestock immunology and applied poultry and swine breeding and genetics. She also serves as a graduate faculty member in the graduate major programs of animal breeding and genetics, bioinformatics and computational biology, genetics, and immunobiology. Research Dr. Lamonts area of research is molecular genetics and immunogenetics of poultry, including the identification of molecular markers and genes controlling bacterial resistance, antibody kinetics, growth, body composition, skeletal integrity and other biological traits; physiological genetics; gene expression; and the major histocompatibility complex genes.
It is generally accepted that antigens in the cytoplasm are loaded in the endoplasmic reticulum and presented at the cell surface on major histocompatibility complex (MHC) class I molecules, whereas peptides present in endo/phagocytic compartments are presented on MHC class II molecules ...
The article is a survey of the cellular interactions in the humoral response to antigen, the role of the major histocompatibility complex in the response, and the antibody response to antigens under the control of histocompatibility-linked immune response (Ir) genes. The article includes chapters on hapten-carrier effects and on the role of the major histocompatibility complex in T- and B-cell co-operation. Furthermore, macrophage-T-cell interactions, T-T cell interactions, and T-cell-macrophage-B-Cell interactions are discussed. There are 84 references.
Ozato, K; Epstein, S L.; Henkart, P; Hansen, T H.; and Sachs, D H., Studies on monoclonal antibodies to mouse mhc products. (1981). Subject Strain Bibliography 1981. 1766 ...
Autori: Sitaru AG, Timmermann W, Ulrichs K, Otto C.. Editorial: Hum Immunol, 2004.. Rezumat:. The indirect alloimmune response seems to be restricted to a few dominant major histocompatibility complex (MHC)-derived peptides responsible for T-cell activation in allograft rejection. The molecular mechanisms of indirect T-cell activation have been studied using peptide analogues derived from the dominant allopeptide in vitro, whereas the in vivo effects of peptide analogues have not been well characterized yet. In the present study, we generated allochimeric peptide analogues by replacing the three allogeneic amino acids 5L, 9L, and 10T in the sequence of the dominant MHC class I allopeptide P1. These allochimeric peptide analogues were used to define the allogeneic amino acids critical for the MHC binding and TCR recognition. We found that position 5 (5L) of the dominant allopeptide acts as an MHC-binding residue, while the other two allogeneic positions, 9 and 10, are important for the T-cell ...
Dr. Tobias Lenz, Group Leader, Max Planck Institute for Evolutionary Biology, Germany. Abstract: An optimal immune response requires a delicate balance of maximizing pathogen recognition while minimizing damage to own tissue by the activated immune machinery. In vertebrates, this process is mediated by the highly polymorphic major histocompatibility complex (MHC), whose molecules present both self and foreign peptides for recognition by immune effector cells. This leads to a quantitative trade-off: Presenting many peptides is good for pathogen resistance but also increases the risk of autoimmunity. Here I present the underlying conceptual framework as well as empirical data elucidating both sides of this trade-off. Population-level computational analysis as well as data from HIV patients support pathogen-mediated selection for increased individual MHC diversity. On the other hand I will show evidence for a positive association between individual MHC diversity and risk for autoimmunity as well as ...
histocompatibility antigen 37: from T1a region of H-2d mouse MHC; amino acid sequence given in first source; related to histocompatibility antigen T10c
T-cell cross-reactivity is essential for effective immune surveillance, but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focussed antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8+ T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase (hTERT). The ILA1 TCR contacted its pMHC with a broad peptide-binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding , the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts ...
T-lymphocyte activation relies on the cognate recognition by the TCR of the MHC-associated peptide ligand (pMHC) presented at the surface of an antigen-presenting cell (APC). This leads to the dynamic formation of a cognate contact between the T lymphocyte and the APC: the immune synapse (IS). Engagement of the TCR by the pMHC in the synaptic zone induces a cascade of signaling events leading to phosphorylation and dephosphorylation of proteins and lipids, which ultimately shapes the response of T lymphocytes. Although the engagement of the T-cell receptor (TCR) takes place at the plasma membrane, the TCR/CD3 complexes and the signaling molecules involved in transduction of the TCR signal are also present in intracellular membrane pools. These pools, which are both endocytic and exocytic, have tentatively been characterized by several groups including ours. We will herein summarize what is known on the intracellular pools of TCR signaling components. We will discuss their origin and the mechanisms
Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells ...
T-cell cross-reactivity is essential for effective immune surveillance, but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focussed antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8+ T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase (hTERT). The ILA1 TCR contacted its pMHC with a broad peptide-binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding , the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts ...
Classically allergens are peptides, presented by the MHC to a T cell receptor. But most of the molecules that cause contact dermatitis are not peptides. One model to explain this phenomenon is that dermatitis-causing chemicals could bind, covalently or not, to peptides that bind to MHCs, then get presented to T cells. But a new study suggests an alternative, MHC-independent route.. In research appearing in Science Immunology, Nicolai and colleagues screened numerous chemicals for contact allergenicity through CD1, a class of proteins that resemble MHCs in structure and function but have more hydrophobic antigen presentation structures. They found that CD1 can present hydrophobic antigens to T cells, and ordinarily presents lipids from the plasma membrane, such as species of PC, PI, DAG and sphingomyelins. A series of crystal structures shows that bulky industrial lipids such as farnesol, which is used in cosmetics and perfumes, appear able to displace these self-lipids. The authors observed ...
For additional information, review our Privacy Policy. aAPCs provide three key signaling components: (i) major histocompatibility complex I/T cell receptor (MHC I/TCR) stimulatory signal, (ii) cluster of differentiation 80/cluster of differentiation 28 (CD80/CD28) costimulatory signal, and (iii) … Monoclonal antibodies against epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been used as single agent therapy in advanced disease for patients with wild type KRAS and NRAS tumors. KEYNOTE 028 was a phase II study that included metastatic CRC patients with or without MMR deficiency. Tumors can manipulate cytokines that promote T regulatory cells and myeloid derived suppressor cells to inhibit cytotoxic T cell function. Clinical trials using Sipuleucel-T have demonstrated a survival benefit in PCa patients, suggesting that this cancer is linked to a … The purpose of this trial is to explore preclinical data that showed that oxaliplatin-containing chemotherapy in ...
Dolton G, Lissina A, Skowera A, Ladell K, Tungatt K, Jones E, Kronenberg-Versteeg D, Akpovwa H, Pentier J, Holland C, Godkin A, Cole D, Neller M, Miles J, Sewell A. Comparison of peptide-major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T-cells. Clin Exp Immunol, 2014, 177 (1).. Estorninho M, Gibson V, Kronenberg-Versteeg D, Ni C, Cerosaletti K, Peakman M. Tracking antigen-experienced CD4 T-cells via tandem deep and shallow T-cell receptor clonotyping. Journal of Immunology, 2013, 191 (11).. Leung R, Simmons A, Proitis P, Guntert A, Kronenberg D, Pritchard M, Tsolaki M, Mecocci P, Kloszwska I, Vellas B, Soininen H, Wahlund LO, Lovestone S. Inflammatory proteins in plasma are associated with severity of Alzheimers disease. PLOS One, 2013, 8 (6).. Knight RR, Kronenberg D, Zhao M, Huang GC, Bulek A, Woolridge L, Cole DK, Sewell AK, Peakman M, Skowera A. Human β-cell killing by autoreactive preproinsulin-specific CD8 T cells is predominantly ...
Cell surface major histocompatibility complex class II proteins are regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes simplex virus 1 ...
Presentation of a protein antigen to T cells is believed to follow its intracellular breakdown by the antigen-presenting cell, with the fragments constituting the trigger of immune recognition. It should then be expected that T-cell recognition of protein antigens in vitro will be independent of protein conformation. Three T-cell lines were made by passage in vitro with native lysozyme of T cells from two mouse strains (B10.BR and DBA/1) that had been primed with the same protein. These cell lines responded well to native lysozyme and very poorly to unfolded (S-sulphopropyl) lysozyme. The response of the T-cell lines to the antigen was major histocompatibility complex (MHC)-restricted. A line from B10.BR was selected for further studies. This line responded to the three surface-simulation synthetic sites of lysozyme (representing the discontinuous antigenic, i.e. antibody binding, sites) and analogues that were extended to a uniform size by a nonsense sequence. T-cell clones prepared from this ...