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Identification of a Novel UTY‐Encoded Minor Histocompatibility Antigen
Author(s) -
Mortensen B. K.,
Rasmussen A. H.,
Larsen M. E.,
Larsen M. V.,
Lund O.,
Braendstrup P.,
Harndahl M.,
Rasmussen M.,
Buus S.,
Stryhn A.,
Vindeløv L.
Publication year - 2012
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2012.02708.x
Subject(s) - minor histocompatibility antigen , human leukocyte antigen , cd8 , cytotoxic t cell , biology , transplantation , immunology , peptide , antigen , microbiology and biotechnology , major histocompatibility complex , genetics , medicine , in vitro , biochemistry
Minor histocompatibility antigens (mHags) encoded by the Y‐chromosome (H‐Y‐mHags) are known to play a pivotal role in allogeneic haematopoietic cell transplantation (HCT) involving female donors and male recipients. We present a new H‐Y‐mHag, YYNAFHWAI (UTY 139–147 ), encoded by the UTY gene and presented by HLA‐A*24:02. Briefly, short peptide stretches encompassing multiple putative H‐Y‐mHags were designed using a bioinformatics predictor of peptide‐HLA binding, NetMHCpan. These peptides were used to screen for peptide‐specific HLA‐restricted T cell responses in peripheral blood mononuclear cells obtained post‐HCT from male recipients of female donor grafts. In one of these recipients, a CD8+ T cell response was observed against a peptide stretch encoded by the UTY gene. Another bioinformatics tool, HLArestrictor, was used to identify the optimal peptide and HLA‐restriction element. Using peptide/HLA tetramers, the specificity of the CD8+ T cell response was successfully validated as being HLA‐A*24:02‐restricted and directed against the male UTY 139–147 peptide. Functional analysis of these T cells demonstrated male UTY 139–147 peptide‐specific cytokine secretion (IFNγ, TNFα and MIP‐1β) and cytotoxic degranulation (CD107a). In contrast, no responses were seen when the T cells were stimulated with patient tumour cells alone. CD8+ T cells specific for this new H‐Y‐mHag were found in three of five HLA‐A*24:02‐positive male recipients of female donor HCT grafts available for this study.