A new MHC locus that influences class I peptide presentation.

We have investigated the HLA-B27-restricted CTL response to HY minor histocompatibility antigens in rats and mice transgenic for HLA-B27 and human beta2-microglobulin. A polymorphism was found at a locus within the H2 complex, producing two distinct but overlapping sets of B27-presented HY peptides. The locus, named Cim2, mapped between the K and Pb loci, and its product is therefore distinct from TAP, LMP, and tapasin. Identical findings in rats and mice, including identical HY peptide sequences and the failure of a rat Tap2A transgene to alter CTL recognition, suggest that a homologous locus with similar polymorphism exists in the rat. Cim2, or a closely linked locus, was found to exert a broad effect on peptide loading of both HLA-B27 and mouse class I alleles. The data thus establish a strong, previously unrecognized MHC-encoded influence on the class I antigen pathway.