Population study of allelic diversity in the human MHC class I-related MIC-A gene.

The polymorphism of major histocompatibility complex (MHC) class I HLA-A, -B, and -C molecules may have evolved through pathogen-driven selection of alleles with diverse peptide-binding specificities. Two MHC-encoded molecules that are distantly related to class I, MIC-A and MIC-B, do not function in the presentation of pathogen-derived peptides to T cells with alphabeta T-cell receptors (TCRs), but are broadly recognized by intraepithelial T cells with gammadelta TCRs. However, both MIC-A and MIC-B are polymorphic, displaying an unusual distribution of a number of variant amino acids in their extracellular alpha1, alpha2, and alpha3 domains. In order to further define the polymorphism of MIC-A, we examined its alleles among 275 individuals with common and rare HLA genotypes. Of 16 previously defined alleles, 12 were confirmed and 5 new alleles were identified. A two-by-two analysis of MIC-A and HLA-B alleles uncovered a number of statistically significant associations. These results confirm and extend previous knowledge on the polymorphism of MIC-A. The strong positive linkage of certain MIC-A and HLA-B alleles may have implications for studies related to MHC-associated diseases and transplantation.