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 nonclassicalMHC class I genes. A distinct family ofMHC class I genes has been recently identified within the humanMHC class I region. TheMICA (MHC classI chain-relatedA) gene in this family is a highly divergent member of theMHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular α1, α2, and α3 domains of theMICA gene from twentyHLA 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 ofMICA alleles is sixteen. Interestingly, a tentative superimposition ofMICA variable residues on theHLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.