Allelic repertoire of the human MHC class I MICA gene

The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression, We have sequenced exons encoding the extracellular alpha 1, alpha 2, and alpha 3 domains of the MICA gene from twenty HLA homozygous typing cell Lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions, Thus, the total number of MICA alleles is sixteen, Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding deft, apparently bordering an invariant ligand binding site.