THE BIOLOGIC IMPORTANCE OF CONSERVED MAJOR HISTOCOMPATIBILITY COMPLEXCLASS-II MOTIFS IN PRIMATES

Phylogenetic comparisons of polymerphic second-exon sequences of MHC c lass II DRB genes showed that equivalents of the HLA-DRB1()03 alleles are present in various nonhuman primate species such as chimpanzees, gorillas, and rhesus macaques. These alleles must root from ancestral structure(s) that were once present in a progenitor species that lived about 35 million years ago. Due to accumulation of genetic variation, however, sequences that cluster into a lineage are generally unique t o a species, To investigate the biologic importance of such conservati on and variation, the peptide-binding capacity of various Mhc-DRB1()0 3 lineage members was studied. Primate Mhc-DRB1()03 lineage members s uccessfully binding the p3-13 peptide of the 65-kD heat-shock protein of Mycobacterium tuberculosis/leprae share a motif that maps to the fl oor of the peptide-binding site. Apart from that, some rhesus macaque MHC class-II-positive cells were able to present the p3-13 peptide to HLA-DR17-restricted T cells whereas cells obtained from great ape spec ies failed to do so. Therefore, these studies open ways to understand which MHC polymorphisms have been maintained in evolution and which MH C residues are essential for peptide binding and T-cell recognition.