Identification of HLA class II-restricted HY-specific T-helper epitope evoking CD4+ T-helper cells in HY-mismatched transplantation
E Spierings, CJ Vermeulen, MH Vogt, LEE Doerner… - The Lancet, 2003 - thelancet.com
E Spierings, CJ Vermeulen, MH Vogt, LEE Doerner, JHF Falkenburg, T Mutis, E Goulmy
The Lancet, 2003•thelancet.comBackground 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 (HY). 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 HY-specific T-helper cells in these transplant settings. Methods HY-specific MHC …
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 (HY). 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 HY-specific T-helper cells in these transplant settings. Methods HY-specific MHC …
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 VIKVNDTYQI presented by HLA-DRβ3*0301. These T-helper cells mature dendritic cells and enhance expansion of minor histocompatibility antigen-specific MHC class Irestricted 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.
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