IDENTIFICATION OF CLASSICAL MINOR HISTOCOMPATIBILITY ANTIGEN AS CELL-DERIVED PEPTIDE

HISTOCOMPATIBILITYantigens expressed on tissue grafted between individuals are recognized by host T cells, which reject the graft1,2. The major histocompatibility complex (MHC) antigens have been identified on the molecular level, whereas the molecules representing the remaining ones, the minor histocompatibility antigens, are unknown, apart from some exceptions3-5. The cytotoxic T lymphocyte (CTL) response against minor histocompatibility antigens shares many aspects with that against virus-infected cells6,7. Virus-specific CTL recognize peptides derived from viral proteins produced in the infected cell. These peptides are presented by MHC class I molecules, as indicated by functional and crystallographic data8,9. By analogy, minor histocompatibility antigens have been postulated to be peptides derived from normal cellular proteins presented by MHC class I molecules10-12. Here we report that peptides derived from normal cellular proteins can indeed be recognized by CTL raised in the classical minor histo-incompatible mouse strain combination, C57BL/6 against BALB.B. Thus, we have proven the above postulate, and isolated one of the minor histocompatibility molecules elusive for several decades. © 1990 Nature Publishing Group.