Journal article
Identification of a Novel UTY‐Encoded Minor Histocompatibility Antigen : Identification of a novel mHag
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.
Language: | English |
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Year: | 2012 |
Pages: | 141-150 |
ISSN: | 13653083 , 03009475 and 03016323 |
Types: | Journal article |
DOI: | 10.1111/j.1365-3083.2012.02708.x |
ORCIDs: | Lund, Ole , 0000-0001-8363-1999 and 0000-0002-4581-3553 |