• This is due to the fact that most tumors are positive for MHC class I but negative for MHC class II, and CD8+ cytotoxic T lymphocytes (CTLs) are able to induce tumor killing upon direct recognition of peptide antigens presented by the tumor's MHC class I molecules. (wikipedia.org)
  • I have used structural biology to explain pre-T-cell receptor (TCR) self-association in T-cell development, and how the TCR specifically recognises polymorphic Human Leukocyte Antigen (HLA) molecules in the context of viral immunity and aberrant T-cell reactivity. (cardiff.ac.uk)
  • To facilitate the discrimination, all nucleated cells present a selection of the peptides contained in their proteins on the cell surface in complex with Major Histocompatibility Complex class I (MHC class I) molecules. (biomedcentral.com)
  • Once inside the ER, the peptides may bind to MHC class I molecules, which are subsequently transported to the cell surface, where the complexes may be recognized by passing CTLs. (biomedcentral.com)
  • One class of non-self molecules are called antigens (short for anti body gen erators) and are defined as substances that bind to specific immune receptors and elicit an immune response. (wikidoc.org)
  • Chimeric antigen receptors (CAR)-engineered T cells have demonstrated remarkable efficacy in patients with B-cell malignancies. (unimedizin-mainz.de)
  • Second, T cell therapies using Tregs (either polyclonal, antigen-specific, or genetically engineered to express chimeric antigen receptors) to establish active dominant immune tolerance or T cells (engineered to express chimeric antigen receptors) to delete pathogenic immune cells. (frontiersin.org)
  • There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. (biomedcentral.com)
  • Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel immunotherapy which modifies T cells with CAR, an artificial fusion protein that incorporates an extracellular antigen recognition domain, a transmembrane domain, and an intracellular domain including costimulation and signaling components [ 4 , 5 ]. (biomedcentral.com)
  • Using HLA-A2.1 transgenic mice, we have demonstrated the feasibility of T-cell receptor (TCR) gene transfer into T cells to circumvent self-tolerance to the widely expressed human p53 and MDM2 TAAs. (unimedizin-mainz.de)
  • Modified peptides showed enhanced binding to HLA-A2 compared with the native sequences and immunization of HLA-A2 transgenic mice generated high avidity modification specific CD8 responses that killed peptide expressing target cells. (bmj.com)
  • The crystal structure of human and murine T cell receptors (TcRs) specific for immunodominant viral peptides presented to cytotoxic T cell (CTL) suggests that the central region of the peptide is critical for TcR contacts and that aromatic rings are accommodated in a small cavity determined by the variable CDR3 region of the TcR ( 7 , 8 ). (silverchair.com)
  • This latter concept has been proposed based on aminoacid sequence homologies and/or immune cross-reactivity between viral and -cell epitopes [8]. (healthweblognews.info)
  • CD4+ T cells promote anti-tumor immunity through numerous mechanisms, including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function. (wikipedia.org)
  • furthermore, recent reports suggest that immunization (using either adjuvant or dendritic cells with pure tumor peptides) can result in productive anti-tumor immunity that is restricted by MHC class I. Finally, elimination of CD8+ T cells from mice at least partially abrogates anti-tumor immunity induced by most cancer vaccines. (wikipedia.org)
  • I have pioneered our molecular understanding of lipid-based immunity by T cells, revealing that it can differ fundamentally from peptide-mediated adaptive immunity. (cardiff.ac.uk)
  • 2023. CD4+ T cell-mediated recognition of a conserved cholesterol-dependent cytolysin epitope generates broad antibacterial immunity . (cardiff.ac.uk)
  • Gene modified dendritic cells (DC) are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. (biomedcentral.com)
  • Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells. (shengsci.com)
  • These mechanisms include antimicrobial peptides called defensins , phagocytosis , and the complement system . (wikidoc.org)
  • Antigen gene transfer to cultured human dendritic cells using recombinant avipoxvirus vectors. (lookformedical.com)
  • Advances in understanding the role of dendritic cells (DCs) as the major antigen (Ag)-presenting cell type of the immune system combined with the recent development of methods for the ex vivo expansion of human DCs have opened the possibility for the transfer of tumor Ags to DCs with a view toward tumor immunotherapy. (lookformedical.com)
  • We successfully applied this strategy to the human TAAs p53, gp100 and MDM2-specific TCRs as promising antigens-driven immunotherapy for both melanoma and hematologic malignancies. (unimedizin-mainz.de)
  • This joint (Frankfurt/Mainz, Dresden, Essen, Heidelberg) translational immunotherapy project aims to combine NK cells as effector cells with universal epitope-specific CAR (UniCAR) with tunable activity. (unimedizin-mainz.de)
  • Because of these encouraging results, we applied the same antigenic strategy to TACA-containing glycopeptides because induction of a degenerate T cell response against this class of tumor antigens may be of great advantage in cancer immunotherapy ( 10 - 12 ). (silverchair.com)
  • I have unearthed structural mechanisms of HLA polymorphism impacting on drug and food hypersensitivities, as well as Natural Killer cell receptor recognition. (cardiff.ac.uk)
  • Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. (biomedcentral.com)
  • To induce CD8+ cytotoxic T lymphocytes (CTLs) along with neutralizing antibody and CD4+ T cell help, a live canarypox virus construct expressing gp120, transmembrane gp41, the gag and protease genes, and sequences containing CTL epitopes in nef and pol was given simultaneously with, or followed by, rgp120 SF2. (lookformedical.com)
  • Homocitrullination occurs in the tumor microenvironment and CD4-mediated immune responses to Hcit epitopes can target stressed tumor cells and provide a potent antitumor response in mouse models. (bmj.com)
  • CAR T cell therapy for hematological cancers can be highly effective, but is currently limited to antigens that are only expressed by tumor cells or by lineages that are non-essential. (acir.org)
  • Targeting antigens expressed by all tumor cells is often associated with on-target/off-tumor toxicities to normal hematopoietic cells. (acir.org)
  • In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc- O -serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. (silverchair.com)
  • Superimposing the amino acids relevant for binding to the BC8 CAR onto the crystal structure of the CD45 extracellular domain revealed a conformational epitope. (acir.org)
  • Methods Homocitrullinated peptides were identified and assessed in vitro for HLA-A2 binding and in vivo in human leukocyte antigen (HLA) transgenic mouse models for immunogenicity. (bmj.com)
  • In the present study, sequences of 40 CD8 + T cell epitope candidates, including previously and newly identified, obtained from Jeryl-Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. (mdpi.com)
  • However, high-avidity T cells specific for tumor-associated antigens (TAAs) are usually absent in patients because of self-tolerance. (unimedizin-mainz.de)
  • Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)
  • Even though CD4+ T cells are known to play a central role in regulating virtually all antigen-specific immune responses, the role they play in immune responses to tumor antigens has not been widely studied compared to that of CD8+ T cells. (wikipedia.org)
  • One patient simultaneously developed CD8+ T cells to HLA-A1-restricted peptide 168-176. (wikipedia.org)
  • citation needed] Clinical vaccination studies using full-length recombinant proteins have the advantage that this form of antigen potentially includes the full range of epitopes for CD4+ and CD8+ T T cells. (wikipedia.org)
  • Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. (bvsalud.org)
  • Background Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. (bmj.com)
  • Allogeneic-donor-derived cells can be genetically modified to eliminate expression of HLA-A. (ashpublications.org)
  • HLA-A disruption from donor cells is a step toward generating allogeneic cells as an off-the-shelf therapeutic. (ashpublications.org)
  • Long-term engraftment of allogeneic cells necessitates eluding immune-mediated rejection, which is currently achieved by matching for human leukocyte antigen (HLA) expression, immunosuppression, and/or delivery of donor-derived cells to sanctuary sites. (ashpublications.org)
  • Transduction of CAR45 into a mixed population of T cells with or without epitope editing of CD45, resulted in the elimination of non-edited cells and enrichment of edited cells. (acir.org)
  • To overcome this, the researchers used the same epitope base editing in human CD34 + hematopoietic stem and precursor cells (HSPC), to protect them from CAR45 BE killing. (acir.org)
  • To determine whether these epitope-edited HSPC and their progeny were resistant to killing by CAR45 BE , NSG mice were engrafted with epitope-edited CD34 + HSPC, injected with MOLM14 AML cells, and treated with CAR45 BE . (acir.org)
  • Finally, the researchers hypothesized that epitope editing could also protect cells from bispecific T cell engagers (BTE) targeting CD45. (acir.org)
  • HLA-identical sibling stem cells are used for the treatment of patients suffering from various hematologic malignant and nonmalignant diseases. (ashpublications.org)
  • We conducted a pilot randomized phase I trial in PC patients to determine the peptide dose required to induce an optimal CD8 + T cell response. (bmj.com)
  • Two main advantages of BCMA as an antigen for CAR-T therapy are the potential reduction of on-target/off-tumor toxicity and the lack of antigen-dependent reduction in CAR-T cell expansion [ 16 ]. (biomedcentral.com)
  • Importantly, in vivo the homocitrullinated aldolase specific response was associated with efficient CD8 dependent antitumor therapy of the aggressive murine B16 tumor model indicating that this epitope is naturally presented in the tumor. (bmj.com)
  • Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. (mdpi.com)
  • In addition, it is likely that protein vaccination leads to presentation of epitopes in the context of various HLA alleles, and therefore this type of vaccine should be applicable to any patient regardless of HLA restriction. (wikipedia.org)
  • Reliable predictions of immunogenic peptides can minimize the experimental effort needed to identify new epitopes to be used in, for example, vaccine design or for diagnostic purposes. (biomedcentral.com)
  • MHC class I ligands are recruited from the cytosolic peptide pool, whose size is likely to depend on the balance between peptide generation by the proteasome and peptide degradation by downstream peptidases. (elsevierpure.com)
  • Recently my team has provided a structural basis of how vitamin B metabolites can be presented and recognised by the immune system, revealing a new class of antigen. (cardiff.ac.uk)
  • The most restrictive step involved in antigen presentation is binding of the peptide to MHC class I. It is estimated that only 1 out of 200 peptides will bind a given MHC class I allele with sufficient strength to elicit a CTL response [ 9 ]. (biomedcentral.com)
  • In fact, our preliminary studies using trinitrophenyl (TNP) as a hapten model, suggested that K b -restricted peptides haptenated in position 4 in 8 mers or position 5 in 9 mers induced a TNP-specific CTL repertoire whose TcR was poorly dependent on MHC class I contacts and highly degenerate ( 9 ). (silverchair.com)
  • 2023. Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02 . (cardiff.ac.uk)
  • Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. (mdpi.com)
  • NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein. (biomedcentral.com)
  • Human tumor samples were analyzed by targeted mass spectrometry for presence of homocitrullinated peptides. (bmj.com)
  • In addition, the homocitrullinated aldolase epitope was also detected in human tumor samples. (bmj.com)
  • Human pDC do not express lineage specific markers, but are characterized by the expression of HLA-DR, CD4, CD123, BDCA2 and BDCA4 [ 3 ]. (biomedcentral.com)
  • We asked what fraction of this pool is available for presentation, and how the size of this fraction is modulated by peptide affinity for the TAP transporters. (elsevierpure.com)
  • We show that presentation varies strongly according to TAP affinities of the epitope precursors. (elsevierpure.com)
  • The fraction of cytosolic peptides recruited for MHC presentation does not exceed 1% and is more than two logs lower for peptides with very low TAP affinities. (elsevierpure.com)
  • The UniCAR is only activated upon cross-linking through a soluble tumor-targeting module carrying the UniCAR binding epitope, thereby achieving highest tumor specificity. (unimedizin-mainz.de)
  • citation needed] In contrast, of eight patients from the second cohort vaccinated with MAGE-3 protein and adjuvant, seven developed high-titered antibodies to MAGE-3, and four had a strong concomitant CD4+ T cell response to HLA-DP4-restricted peptide 243-258. (wikipedia.org)
  • CAP1-6D, an altered peptide ligand can help bypass tolerance. (bmj.com)
  • Conclusions The T cell response in this randomized phase I trial was dose-dependent with the 1 mg CEA peptide dose eliciting the most robust T cell responses. (bmj.com)
  • Results Homocitrullinated peptides from aldolase and cytokeratin were identified, that stimulated CD8-mediated responses in vivo. (bmj.com)
  • The inclusion of CD4+ epitopes into MAGE-3 vaccination studies has recently been facilitated by the identification of several HLA-DR-restricted and one HLA-DP4-restricted epitope. (wikipedia.org)
  • We use two evaluation datasets consisting of known HIV CTL epitopes and their source proteins. (biomedcentral.com)
  • However, limited data are available about sequence variability in CD8 + T cell epitope regions of mumps virus (MuV) proteins. (mdpi.com)
  • Namely, recipients sharing one or more HLA Ags with their cord blood donor inherited paternal Ags had reduced relapse rates compared with those who did not. (ashpublications.org)
  • 2023. CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms . (cardiff.ac.uk)
  • Several other groups have likewise attempted to generate methods that enable CTL epitope identification. (biomedcentral.com)
  • Methods Patients with a PS 0-1, HLA-A2+ and CEA-expressing, previously-treated PC were randomized to receive 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C) of CEA peptide emulsified in Montanide and GM-CSF, given every 2 weeks until disease progression. (bmj.com)
  • At least four other methods have been developed recently that likewise attempt to predict CTL epitopes: EpiJen, MAPPP, MHC-pathway, and WAPP. (biomedcentral.com)
  • In the RANK measure, we compare two methods at a time and count how often each of the methods rank the epitope highest. (biomedcentral.com)
  • To overcome fratricide, the researchers aimed to identify a non-synonymous mutation at a CD45-relevant epitope using CRISPR base editing, so that CAR45 would not recognize it, while simultaneously maintaining the expression and function of CD45. (acir.org)
  • Of nine patients in the first cohort, three developed marginal antibody titers and another one had a CD8+ T cell response to HLA-A2-restricted peptide MAGE-3 271-279. (wikipedia.org)
  • A model epitope restricted by HLA-A2 and a series of epitope precursors with N-terminal extensions by single residues modifying TAP affinity were expressed in a system that allowed us to monitor and modulate cytosolic peptide copy numbers. (elsevierpure.com)
  • Additionally, a comprehensive overview of antigen selection is presented along with preliminary results and future directions of CAR-T therapy development. (biomedcentral.com)
  • These results demonstrate that Abs recognizing MAP3865c epitopes cross-react with ZnT8, possibly Alpl underlying a molecular mimicry mechanism, which may precipitate T1D in MAP-infected individuals. (healthweblognews.info)
  • Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons. (mdc-berlin.de)