Domain structures and molecular evolution of class I and class II major histocompatibility gene complex (MHC) products deduced from amino acid and nucleotide sequence homologies.

Domain structures of class I and class II MHC products were analyzed from a viewpoint of amino acid and nucleotide sequence homologies. Alignment statistics revealed that class I (transplantation) antigen H chains consist of four mutually homologous domains, and that class II (HLA-DR) antigen beta and alpha chains are both composed of three mutually homologous ones. The N-terminal three and two domains of class I and class II (both beta and alpha) gene products, respectively, all of which being approximately 90 residues long, were concluded to be homologous to beta2-microglobulin (beta2M). The membrane-embedded C-terminal shorter domains of these MHC products were also found to be homologous to one another and to the third domain of class I H chains. Class I H chains were found to be more closely related to class II alpha chains than to class II beta chains. Based on these findings, an exon duplication history from a common ancestral gene encoding a beta2M-like primodial protein of one-domain-length up to the contemporary MHC products was proposed.