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The Human UTY Gene Encodes a Novel HLA-B8-Restricted H-Y Antigen¹

Edus H. Warren^2,3,*,, Marc A. Gavin^3,*, Elizabeth Simpson^¶, Phillip Chandler^¶, David C. Page^||, Christine Disteche^§, Kimberly A. Stankey^*, Philip D. Greenberg^*,, and Stanley R. Riddell^*,

^* Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Departments of Medicine, Immunology, and ^§ Pathology, University of Washington School of Medicine, Seattle, WA 98195; ^¶ Transplantation Biology Section, Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom; and ^|| Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142

The mammalian Y chromosome encodes male-specific minor histocompatibility (H-Y) Ags that are recognized by female T cells in an MHC-restricted manner. Two human H-Y epitopes presented by HLA-A2 and HLA-B7, respectively, have been identified previously and both are derived from the SMCY gene. We previously isolated CD8⁺ CTL clones that recognized a male-specific minor histocompatibility Ag presented by HLA-B8. In contrast to the SMCY-encoded H-Y epitopes, the B8/H-Y Ag was not presented by fibroblasts from male donors, suggesting that it was encoded by a novel gene. We now report that the HLA-B8-restricted H-Y epitope is defined by the octameric peptide LPHNHTDL corresponding to aa residues 566–573 of the human UTY protein. Transcription of the UTY gene is detected in a wide range of human tissues, but presentation of the UTY-derived H-Y epitope to CTL by cultured human cells shows significant cell-type specificity. Identification of this CTL-defined H-Y epitope should facilitate analysis of its contribution to graft/host interactions following sex-mismatched organ and bone marrow transplantation.