STRUCTURE, FUNCTION, AND EVOLUTION OF MOUSE TL GENES, NONCLASSICAL CLASS-I GENES OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

In contrast to well-studied ''classical'' class I genes of the major h istocompatibility complex (MHC), the biology of nonclassical class I g enes remains largely unexamined. The mouse TL genes constitute one of the best defined systems among nonclassical class I genes in the T reg ion of the MHC. To elucidate the function and the evolution of TL gene s and their relationship to classical class I genes, seven TL DNA sequ ences, including one from a Japanese wild mouse, were examined and com pared with those of several mouse and human classical class I genes. T he TL genes differ from either classical class I genes or pseudogenes in the extent and pattern of nucleotide substitutions. Natural selecti on appears to have operated so as to preserve the function of TL, whic h might have been acquired in an early stage of its evolution. In a pu tative peptide-binding region encoded by TL genes, the rate of nonsyno nymous (amino acid replacing) substitution is considerably lower than that of synonymous substitution. This conservation is completely oppos ite that In classical class I genes, in which the peptide-binding regi on has evolved to diversify amino acid sequences so as to recognize a variety of antigens. Thus, it is suggested that the function of TL ant igens is distinct from that of classical class I antigens and is relat ed to the recognition of a relatively restricted repertoire of antigen s and their presentation to T-cell receptors.