Identification of classical minor histocompatibility antigen as cell-derived peptide

Abstract

HISTOCOMPATIBILITYantigens expressed on tissue grafted between individuals are recognized by host T cells, which reject the graft^1,2. 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 exceptions^3–5. The cytotoxic T lymphocyte (CTL) response against minor histocompatibility antigens shares many aspects with that against virus-infected cells^6,7. 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 data^8,9. By analogy, minor histocompatibility antigens have been postulated to be peptides derived from normal cellular proteins presented by MHC class I molecules^10–12. 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.