Minor histocompatibility antigens

Abstract

Immune responses against foreign tissue or organs can be directed against alloantigenic differences between donor and host encoded by genes of the major histocompatibility complex (MHC; HLA in man and H-2 in mouse). However, when MHC antigens are matched, as in HLA-identical siblings, or between different mouse strains sharing the same H-2 haplotype, graft rejection still occurs and is then directed against alloantigenic differences termed minor histocompatibility (H) antigens. Their molecular nature is not yet determined but they are recognised by T cells in an MHC-restricted manner, so are assumed to be derived from molecules co-expressed with MHC class I or II glycoproteins, possibly as peptides or as "super-antigens". The genes encoding them are scattered throughout the genome, including the Y chromosome, on which the H-Y antigen gene has been mapped in both man and mouse. One striking feature of minor H antigens is their recognition by T cells but not by antibodies. This made work with them, before our ability to generate T cell responses and maintain T cell clones in vitro, very slow but currently the use of MHC-restricted T cell clones has enabled detailed mapping studies and should eventually allow for their molecular characterisation.