Organization and structure of the Qa genes of the major histocompatibility complex of the C3H mouse: Implications for Qa function and class I evolution

Abstract

We have determined the structure and organization of the entire Qa family of class I genes from the major histocompatibility complex of the C3H mouse. Restriction maps of overlapping lambda and cosmid clones reveal that there are only five Qa(k) genes: Q1(k), Q2(k), Q4(k), Q10(k) and a Q5/9 hybrid, presumably generated by unequal homologous recombination. The resulting deletion of Q6-Q9 is consistent with the Qa-2(null) phenotype of this mouse strain. We have sequenced the Qa(k) genes, and predict that each may encode a class I molecule with a structure comparable with that proposed for the transplantation antigens. Furthermore, these Qa products should be able to bind peptides and interact with appropriate T-cell receptors. Interestingly, in comparing Qa(k) and H-2(k) sequences, we find limited evidence of interlocus gene conversion between Qa and H-2 loci, suggesting that the Qa genes are not likely to serve as a reservoir of genetic information for the generation of H-2 diversity within this haplotype.