title: Identification of a novel UTY-encoded minor histocompatibility antigen.
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 (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.
authors.affiliation: Allogeneic Hematopoietic Cell Transplantation Laboratory, Department of Hematology, Rigshospitalet, Copenhagen, Denmark. bokokmortensen@hotmail.com
authors.forename: B K
authors.initials: BK
authors.lastname: Mortensen
authors.forename: A H
authors.initials: AH
authors.lastname: Rasmussen
authors.forename: M E
authors.initials: ME
authors.lastname: Larsen
authors.forename: M V
authors.initials: MV
authors.lastname: Larsen
authors.forename: O
authors.initials: O
authors.lastname: Lund
authors.forename: P
authors.initials: P
authors.lastname: Braendstrup
authors.forename: M
authors.initials: M
authors.lastname: Harndahl
authors.forename: M
authors.initials: M
authors.lastname: Rasmussen
authors.forename: S
authors.initials: S
authors.lastname: Buus
authors.forename: A
authors.initials: A
authors.lastname: Stryhn
authors.forename: L
authors.initials: L
authors.lastname: Vindeløv
mesh_terms: D000595:Amino Acid Sequence; D001773:Blood Cells / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C484453:UTY protein, human