The Human UTY Gene Encodes a Novel HLA-B8-Restricted

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 CD81 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. The Journal of Immunology, 2000, 164: 2807–2814. T he mammalian Y chromosome encodes histocompatibil-ity determinants that trigger rejection of skin grafts frommale mice by syngeneic females (1) and has been impli-cated in the rejection of human bone marrow grafts from MHC-compatible male donors by female recipients (2, 3). In both mice and humans, class I MHC-restricted CTL recognizing male-spe-cific (H-Y)4 Ags have been generated in vitro by secondary mixe