Epitopes described in "Identification of HLA class II-restricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Y-mismatched transplantation."

Article Authors:Eric Spierings; Corine J Vermeulen; Mario H Vogt; Lucie E E Doerner; J H Frederik Falkenburg; Tuna Mutis; Els Goulmy
Article Title:Identification of HLA class II-restricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Y-mismatched transplantation.
Reference Detail
Reference ID:1020137
Abstract:BACKGROUND: Stem-cell grafts between HLA-identical siblings are less likely to succeed when there is a sex mismatch. This lack of success can be interpreted as enhanced activity directed against minor histocompatibility antigens encoded by the Y chromosome (H-Y). So far, in man, only cytotoxic T lymphocytes (CTLs) specific for several minor histocompatibility antigens have been reported. We aimed to identify and clarify the role of MHC class II-restricted H-Y-specific T-helper cells in these transplant settings. METHODS: H-Y-specific MHC class II-restricted CD4+ T cells were isolated from blood of a female patient who rejected an HLA-identical male stem-cell transplant. By molecular cloning of H-Y genes and functional T-helper experiments, we elucidated antigen specificity and the functional properties of these H-Y-specific T-helper cells. FINDINGS: CD4+ T-helper cells recognise the Y gene-encoded peptide VIKVNDTVQI presented by HLA-DRbeta3*0301. These T-helper cells mature dendritic cells and enhance expansion of minor histocompatibility antigen-specific MHC class I-restricted CD8+ CTLs. INTERPRETATION: Characterisation of an MHC class II-restricted H-Y epitope that evoked CD4+ T-helper responses adds a novel cellular component to the alloimmune response against Y chromosome-encoded minor histocompatibility antigens. This component completes the H-Y-directed alloimmune response and aids understanding of the poorer outcome of sex-mismatched transplants.
Affiliations:Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Post-box 9600, 2300 RC, Leiden, Netherlands. eric.spierings@lumc.nl
Reference Type:Literature
PubMed ID:12944060
Journal Volume:362
Article Pages:610-5
Journal ISSN:1474-547X
Article Chemical List:Antigens, CD4;Epitopes, T-Lymphocyte;H-Y Antigen;Histocompatibility Antigens Class II
Article MeSH List:Adult; Anemia, Aplastic(surgery); Antigens, CD4(immunology); Chromosomes, Human, Y(immunology); Epitope Mapping; Epitopes, T-Lymphocyte(immunology); Female; Genes, sry(immunology); Graft Rejection(immunology); H-Y Antigen(immunology); Histocompatibility Antigens Class II(immunology); Humans; Male; Minor Histocompatibility Loci(immunology); Sex Determination Processes; Sex Factors; Stem Cell Transplantation; T-Lymphocytes, Helper-Inducer(immunology); Transplantation Immunology(immunology)
Curation Last Updated:2015-07-22 20:01:28