• The saga of MHC-bound peptides: a renaissance for antigen presentation? (jci.org)
  • HLA-DR molecules were affinity purified and bound peptides acid eluted. (jci.org)
  • For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. (jci.org)
  • This approach can be extended to characterize HLA-bound peptides in various autoimmune settings. (jci.org)
  • peptides bound to HLA-DR17 from bronchoalveolar lavage cells of sarcoidosis patients were analyzed in order to identify target antigens of the autoimmune response (see the related article beginning on page 3576). (jci.org)
  • Residue 34 is located in pocket B and contacts the main chain carbon of bound peptides in HLA-A2. (usda.gov)
  • Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). (aacrjournals.org)
  • 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. (scancell.co.uk)
  • 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. (scancell.co.uk)
  • Peripheral blood mononuclear cells from three HLA-A2 + healthy donors and four E75 peptide-vaccinated patients were stimulated with HER2/neu-derived peptides and tested in standard chromium release cytotoxicity assays with HER2/neu + tumor cells pretreated with trastuzumab. (usuhs.edu)
  • MHC class II genes are mainly expressed on specialized antigen-presenting cells of the immune system, which monitor the extracellular environment and use MHC receptors to present peptides of extracellular pathogens to the T-cells. (biomedcentral.com)
  • Although HLA-mismatched donors can mount high-avidity CTLs against HLA-A2-presented peptides of WT1, a dominant anti-alloimmune response usually obscures detection of peptide-specific CTLs. (ox.ac.uk)
  • Although a limited number of immunodominant peptide epitopes are consistently observed in diseases such as HIV-1 infection, the relationship between immunodominance and antigen processing in humans is largely unknown. (jci.org)
  • crystal structure of htlv-1 tax peptide bound to human class i mhc hla-a2 with the k66a mutation in the heavy chain. (berkeley.edu)
  • Studies with HLA-A2 have shown that changes in residue 34 do not affect viral peptide presentation. (usda.gov)
  • Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. (medscape.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)
  • Single amino acid substitutions were introduced to the CAP1 peptide (YLSGANLNL), an immunogenic HLA-A2 + -binding peptide derived from human carcinoembryonic antigen (CEA). (aacrjournals.org)
  • Scholars@Duke publication: Peptide/MHC tetramer-based sorting of CD8⁺ T cells to a leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire. (duke.edu)
  • From a leukemia cell line, we identified a CDK4-derived peptide epitope, UNC-CDK4-1 (ALTPVVVTL), that bound HLA-A*02:01 with high affinity and could induce CD8⁺ T-cell responses in vitro. (duke.edu)
  • Babatz J, Röllig C, Löbel B, Folprecht G, Haack M, Günther H, Köhne CH, Ehninger G, Schmitz M, Bornhäuser M. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. (nwbio.com)
  • Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. (uni-wuerzburg.de)
  • 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)
  • We report on a 26 patient phase I/II clinical trial (NCT01352286) to investigate the safety, feasibility and anti-tumor activity of T cells engineered to express an affinity-enhanced TCR that recognizes the NY-ESO-1/LAGE-1 peptide complex HLA-A*0201-SLLMWITQC. (biomedcentral.com)
  • Pretreatment of tumor cells with trastuzumab resulted in increases in specific cytotoxicity by peptide-stimulated cytotoxic T lymphocytes from HLA-A2 + donors over untreated cells by an average of 5.6% and 15.3% (P = .0002) for doses of 10 and 50 μg/mL, respectively. (usuhs.edu)
  • Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. (elsevierpure.com)
  • Here we explored the feasibility of using recombinant HLA-A2 monomers containing single peptide epitopes as immunogens to generate peptide-specific CTLs from allogeneic donors. (ox.ac.uk)
  • We demonstrate that the coating of HLA-A2(-) B lymphocytes with A2/peptide monomers provides a strong stimulus for autologous peptide-specific CTLs. (ox.ac.uk)
  • After 3 to 5 rounds of stimulation a population of CD8(+) T cells binding A2/peptide tetramers is easily detectable by fluorescence-activated cell sorting analysis. (ox.ac.uk)
  • Thus, HLA/peptide monomers may be useful to isolate peptide-specific donor lymphocytes for treatment of patients with leukemia after HLA-mismatched transplantation. (ox.ac.uk)
  • Functional analysis employing site directed mutagenesis identified BF amino acid residues forming serologic epitopes as well as residues important in antigen presentation to ALV induced cytotoxic T lymphocytes. (usda.gov)
  • Human cytotoxic T lymphocyte responses to live attenuated 17D yellow fever vaccine: identification of HLA-B35-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3, and the structural protein E. (umassmed.edu)
  • Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. (nwbio.com)
  • Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. (nwbio.com)
  • The immunotherapeutic vaccine OSE-2101 (Tedopi) improved survival by antigen-specific cytotoxic T lymphocytes (CTL) responses in patients with HLA-A2 positive advanced non small cell lung cancer (NSCLC), according to results from a phase II study presented in a poster at the 34th Society for Immunotherapy of Cancer (SITC) Annual Meeting. (targetedonc.com)
  • Recent studies have detected Wilms tumor antigen (WT1)-specific cytotoxic T lymphocytes (CTLs) in patients with acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) and demonstrated that most of these CTLs were low avidity. (ox.ac.uk)
  • Furthermore, sorted A2/WT1 tetramer-positive CTLs display strong cytotoxic activity against leukemia cells expressing WT1 endogenously but not against WT1(-) human tumor cells. (ox.ac.uk)
  • The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. (wikidoc.org)
  • 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. (scancell.co.uk)
  • Broadly recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles. (umassmed.edu)
  • HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy. (cdc.gov)
  • HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients. (cdc.gov)
  • HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy. (cdc.gov)
  • There is a fairly strong genetic background to pemphigus vulgaris with linkage to HLA class II alleles. (bvsalud.org)
  • A cohort of HLA-A2+ NSCLC donors demonstrated that the number of epitope specific CD8+ T cells increased in NSCLC than healthy controls when measured with tetramer derived from the candidate MAGE-A3 epitopes, especially epitope Mp4 (MAGE-A3: 160-169, LVFGIELMEV). (thno.org)
  • BF residues 78 and 81 (HLA 79 and 82) form an antibody epitope with a slight effect on ALV antigen presentation, consistent with their predicted orientation based on the HLA-A2 crystal structure. (usda.gov)
  • because it targeted 9 epitopes from 5 antigens plus an additional epitope. (targetedonc.com)
  • These studies demonstrate that HerpV is a promising immunotherapy candidate for genital herpes, and provide a foundation for evaluating HerpV in human HSV-2(+) subjects with the intent of eliciting CD4(+) and CD8(+) T cell responses to a broad array of viral antigens. (nih.gov)
  • 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)
  • The possibility of interactions between HLA type and outcome should be considered in future immunotherapy trials. (northwestern.edu)
  • TX200 is an autologous (cells collected from the patient) HLA-A2-targeted CAR-Treg cell therapy. (sangamo.com)
  • This phase II trial studies the side effects and how well white blood cells taken from person's own (autologous) cluster of differentiation (CD)8+ antigen-specific T cells, cyclophosphamide, aldesleukin, and ipilimumab work in treating patients with melanoma that has spread to another place in the body. (survivornet.com)
  • Autologous CD8+ antigen-specific T cells are white blood cells that are designed in the laboratory to find melanoma cells and may kill them. (survivornet.com)
  • Giving autologous CD8+ antigen-specific T cells with cyclophosphamide, aldesleukin, and ipilimumab may be an effective treatment for patients with metastatic melanoma. (survivornet.com)
  • Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2 + patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry. (johnshopkins.edu)
  • The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. (medscape.com)
  • The binding of the adenovirus (Ad) protein E3-19K with the human leukocyte antigen (HLA) plays an. (chemaxon.com)
  • BRISBANE, Calif. --(BUSINESS WIRE)--Nov. 19, 2019-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, announced today that the United Kingdom's ( UK ) Medicines Healthcare Products Regulatory Agency (MHRA) has granted authorization of the first-in-human clinical trial to evaluate a Chimeric Antigen Receptor Regulatory T Cell (CAR-Treg) therapy. (sangamo.com)
  • HLA-A2 is a protein belonging to the human leukocyte antigen (HLA) system. (sangamo.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)
  • T1D susceptibility is restored to normally resistant NOD.β2m -/- mice transgenically expressing human disease-associated HLA-A ∗ 02:01 or HLA-B ∗ 39:06 class I molecules in place of their murine counterparts. (elsevierpure.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)
  • In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning. (thno.org)
  • We identified the HLA-A2 restricted T cell epitopes from MAGE-A3 that could effectively induce the activation and cytotoxicity of CD8+ T cells using artificial APC in vitro . (thno.org)
  • We have previously shown that Scandinavian sarcoidosis patients expressing the HLA-DR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4+ T cells expressing the TCR AV2S3 gene segment. (jci.org)
  • This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3+ T cells. (jci.org)
  • To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301pos patients were obtained by bronchoalveolar lavage. (jci.org)
  • A vaccination strategy designed to enhance the immunogenicity of self-antigens that are overexpressed in tumor cells is to identify and slightly modify immunodominant epitopes that elicit T-cell responses. (aacrjournals.org)
  • This line was obtained from peripheral blood mononuclear cells from an HLA-A2 + individual vaccinated with a vaccinia-CEA recombinant. (aacrjournals.org)
  • The patient's regulatory T cells (Tregs), a type of white blood cell which plays a key role in regulating the immune response and inflammation, are collected and genetically engineered with a Chimeric Antigen Receptor (CAR) designed to bind to HLA-A2. (sangamo.com)
  • TX200 HLA-A2 CAR-Treg cells are designed to accumulate and localize within the new kidney where the HLA‑A2 protein is present, thereby utilizing the ability of Tregs to suppress immune responses against the transplanted kidney. (sangamo.com)
  • Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. (nwbio.com)
  • However, high-avidity T cells specific for tumor-associated antigens (TAAs) are usually absent in patients because of self-tolerance. (unimedizin-mainz.de)
  • Chimeric antigen receptors (CAR)-engineered T cells have demonstrated remarkable efficacy in patients with B-cell malignancies. (unimedizin-mainz.de)
  • Evaluate the influence of anti-CTLA4 on the induction of T cells to non-targeted tumor-associated antigens (antigen-spreading) following adoptive transfer antigen-specific CTL, and the correlation of these responses with clinical outcome. (survivornet.com)
  • Thus, the local immunological milieu in tissue compartments forms the nature and magnitude of the host responses, i.e., frequencies of regulatory T cells (Tregs) vs. T-helper 17 (Th17) cells, amount of pro-inflammatory cytokines vs. anti-inflammatory cytokines, extent of neutrophilia and antigen-presenting-cell (APC) activation, among others. (frontiersin.org)
  • 7 patients progressed after day 100, which was accompanied by loss of engineered T cells or loss of tumor antigen. (biomedcentral.com)
  • however, the challenge for T cells is to recognize tumour antigens whilst minimizing cross-reactivity with antigens associated with healthy tissue. (scancell.co.uk)
  • Some tumour cells, including those associated with viral infections, have clear, tumour-specific antigens that can be targeted by T cells. (scancell.co.uk)
  • Diversity of intraepithelial CD8aa T cells that recognize antigens from commensal flora. (elsevierpure.com)
  • We know that at least 1 of these antigens is expressed by the lung cancer cells. (targetedonc.com)
  • Gene modified dendritic cells (DC) are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. (biomedcentral.com)
  • For its lead programme, CAR-T reg cells are designed to target HLA-A2, a common mismatch antigen in transplantation. (european-biotechnology.com)
  • Donor/recipient mismatch in HLA molecules is a primary contributor to organ transplant incompatibility and may ultimately lead to immune-mediated rejection of the transplanted organ. (sangamo.com)
  • However, NOD.β2m -/- mice also lack nonclassical MHC I family members, including FcRn, required for antigen presentation, and maintenance of serum IgG and albumin, precluding therapies dependent on these molecules. (elsevierpure.com)
  • The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigen displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. (wikidoc.org)
  • The recipient's immune system can recognize this HLA-A2 mismatch and may attack the new kidney carrying the HLA-A2 protein, potentially leading to graft rejection. (sangamo.com)
  • Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. (thno.org)
  • The nature of the molecule, that interacts both with the antigens (i.e., the Antigen Binding Sites, onwards ABS) and the cellular and immune system components, makes it subject to different types of natural selection. (biomedcentral.com)
  • Recombinant targeting modules will be based on antibodies and soluble single-chain fragments of TCR specific for melanoma antigens. (unimedizin-mainz.de)
  • An analysis of mature data from S9035 indicates a significant OS benefit from adjuvant vaccine therapy for patients with HLA-A2- and/or HLA-Cw3-expressing melanoma. (northwestern.edu)
  • Further investigations of melanoma-associated antigens present in Melacine and presented by HLA-A2 and HLA-Cw3 may be warranted. (northwestern.edu)
  • Efforts to develop a subunit vaccine against genital herpes have been hampered by lack of knowledge of the protective antigens of HSV-2, the causative agent of the disease. (nih.gov)
  • The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. (medscape.com)
  • They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine. (medscape.com)
  • OSE-2102 is now being studied in the phase III ATALANTE trial, in which the vaccine is being compared with the standard of care in HLA-A2-positive advanced NSCLC. (targetedonc.com)
  • Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes. (bvsalud.org)
  • Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen. (ox.ac.uk)
  • I. Evaluate the influence of anti-CTLA4 on the duration of in vivo persistence and anti-tumor efficacy achieved following adoptive transfer of antigen-specific CTL. (survivornet.com)
  • This work identified candidate TCRs potentially suitable for TCR-T design targeting HLA-A2 restricted MAGE-A3 tumor antigen. (thno.org)
  • Thus, interaction of the pMHC complex with selected Vα-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to Vα 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR. (elsevierpure.com)
  • Transgenic expression of HLA-A2 or-B39 restored pathogenic CD8 + T-cell development and T1D susceptibility to NOD-cMHCI -/- mice. (elsevierpure.com)
  • marrow is monitored for expression of target antigen. (biomedcentral.com)
  • The effects of treatment on relapse-free survival (RFS) and overall survival (OS) were evaluated, and prespecified analyses investigated associations between treatment and HLA expression. (northwestern.edu)
  • There was no impact of HLA-A2 and/or HLA-Cw3 expression on observation arm patients. (northwestern.edu)
  • We used a novel in vitro degradation assay involving cytosolic extracts as well as endogenous intracellular processing assays to examine 2 well-characterized HIV-1 Gag overlapping epitopes presented by the same HLA class I allele, one of which is consistently immunodominant and the other subdominant in infected persons. (jci.org)
  • It's given subcutaneously to the subpopulation of patients that are HLA-A2 positive. (targetedonc.com)
  • Testing of T cell-based cancer therapeutics often involves measuring cancer antigen-specific T-cell populations with the assumption that they arise from in vivo clonal expansion. (duke.edu)
  • Mapping recurrent TCRβ clonotype sequences onto TCRβ repertoires can help confirm or refute antigen-specific T-cell expansion in vivo. (duke.edu)
  • The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients. (medscape.com)
  • We identified UNC-CDK4-1/HLA-A*02:01 tetramer⁺ populations in 3 of 6 patients with acute myeloid leukemia who had undergone allogeneic stem cell transplantation. (duke.edu)
  • Additionally, at the 2019 SITC Meeting, we presented a poster (P339) which showed that patients who develop at least 2 immune responses against antigens have a survival that will be double compared to the other patients. (targetedonc.com)
  • In contrast, a site directed substitution in residue 34 dramatically alters ALV antigen presentation by the BFIV21 class I glycoprotein. (usda.gov)
  • TX200 is being studied for the prevention of immune-mediated rejection following HLA-A2 mismatched kidney transplantation for end-stage renal disease (ESRD). (sangamo.com)
  • This innovative and personalized cellular therapy approach for HLA-A2 mismatched kidney transplantation is designed to help regulate the body's immune system specifically and locally to promote acceptance of an immunologically mismatched donor organ. (sangamo.com)
  • HLA-A2 CAR-T reg cellular therapy targets the prevention of chronic rejection after organ transplantation. (european-biotechnology.com)
  • However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. (thno.org)
  • HerpV is observed to be immunogenic, generating CD4(+) and CD8(+) T cell responses in three mouse strains including HLA-A2 transgenic mice. (nih.gov)
  • Vaccines based either on selected antigens or attenuated live virus approaches have not demonstrated meaningful clinical activity. (nih.gov)
  • This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. (uni-wuerzburg.de)
  • These data indicate that the fine physical structure of chicken class I is similar to HLA along the alpha 1 alpha helix, whereas the side chain orientation of internal residues impacting pocket B are altered. (usda.gov)
  • What was the rationale for the phase III ATALANTE-1 trial of Tedopi versus standard of care in HLA-A2 positive advanced NSCLC? (targetedonc.com)
  • Tedopi was developed in NSCLC because this therapy targets 5 antigens. (targetedonc.com)
  • On one hand, positive selection signals are expected in the ABS as they may evolve to bind novel antigens carried by pathogens, which in turn may evolve to escape recognition. (biomedcentral.com)
  • Nevertheless, the β2 microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome. (wikipedia.org)