Identification of a Novel UTY‐Encoded Minor Histocompatibility Antigen

B. K. Mortensen, A. H. Rasmussen, Malene Erup Larsen, Mette Voldby Larsen, Ole Lund, P. Braendstrup, Mikkel Nors Harndahl, M. Rasmussen, S. Buus, A. Stryhn, Lars Vindeløv

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    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 (UTY139–147), 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 UTY139–147 peptide. Functional analysis of these T cells demonstrated male UTY139–147 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.
    Original languageEnglish
    JournalScandinavian Journal of Immunology
    Volume76
    Issue number2
    Pages (from-to)141-150
    ISSN0300-9475
    DOIs
    Publication statusPublished - 2012

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