Bg. Elferink et al., THE BIOLOGIC IMPORTANCE OF CONSERVED MAJOR HISTOCOMPATIBILITY COMPLEXCLASS-II MOTIFS IN PRIMATES, Human immunology, 38(3), 1993, pp. 201-205
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.