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Title: Identification of a Novel UTY‐Encoded Minor Histocompatibility Antigen
Type: Journal articleJournal article
Participant(s):
Forfatter:  Mortensen, B. K.
Department of Hematology, Rigshospitalet

Forfatter:  Rasmussen, A. H.
Laboratory of Experimental Immunology, University of Copenhagen

Author:  Larsen, Malene Erup (Cwisno: 37406)
Technical University of Denmark

Author:  Larsen, Mette Voldby (Cwisno: 24381)
Technical University of Denmark
Email:

Author:  Lund, Ole (Cwisno: 5094)
Technical University of Denmark
Email:

Forfatter:  Braendstrup, P.
Department of Hematology, Rigshospitalet

Forfatter:  Harndahl, Mikkel Nors
Laboratory of Experimental Immunology, University of Copenhagen

Forfatter:  Rasmussen, M.
Laboratory of Experimental Immunology, University of Copenhagen

Forfatter:  Buus, S.
Laboratory of Experimental Immunology, University of Copenhagen

Forfatter:  Stryhn, A.
Laboratory of Experimental Immunology, University of Copenhagen

Forfatter:  Vindeløv, Lars
Department of Hematology, Rigshospitalet
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.
Published: in journal: Scandinavian Journal of Immunology (ISSN: 0300-9475) (DOI: http://dx.doi.org/10.1111/j.1365-3083.2012.02708.x), vol: 76, issue: 2, pages: 141-150, 2012
DOI:
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