HLA-AR, an inactivated antigen-presenting locus related to HLA-A. Implications for the evolution of the MHC.

Abstract

The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag-presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA-AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes.