Identification of a Novel UTY-Encoded Minor Histocompatibility Antigen

• Published in: Scandinavian journal of immunology 2012-08, Vol.76 (2), p.141-150
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Blood Cells - transplantation; CD8-Positive T-Lymphocytes - immunology; Epitopes - immunology; Female; HLA-A24 Antigen - immunology; Humans; Male; Minor Histocompatibility Antigens - immunology; Nuclear Proteins - chemistry; Nuclear Proteins - immunology; Transplantation, Homologous
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2012.02708.x

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.