ALLELIC DIVERSITY AT THE PRIMATE MHC-DMB LOCUS - PRESENCE OF A CONSERVED TYROSINE INHIBITORY MOTIF IN THE CYTOPLASMIC TAIL

Ten new primate Mhc-DMB complete cDNA sequences have been obtained in chimpanzee (n=four), gorilla (,n=three) and orangutan (n=three); this gene has not been previously studied in these species, Exonic allelism has been recorded all along the molecule domains and also in the lead er peptide, but not in the transmembrane segment. An analysis of the r esidues critical in the conformation oi the Mhc-DR peptide-binding sit e was done in order to look for a Mhc-DR homologue site; synonymous su bstitutions are favoured in this homologous HLA-DM region. This is ano ther finding that supports the possibility that DM could not be typica lly pn presenting molecules. The immunoreceptor inhibition motif Tyr 2 30-Thr/Ser 231-Pro 232-Leu 233 (ITIM) is invariantly present in apes f or at least 15 million years, and may have a double function: 1) To di rect DMB-DMA molecules from the endoplasmic reticulum or cell surface towards the endosomal/lysosomal class II compartment and 2) to send an inhibitory signal to the cell in order to stop synthesis of unnecessa ry HLA-DR molecules, once all available antigenic peptides are loaded. Other molecules, like NK-cell receptors and Fc receptors, bear this t ype of tyrosine-based inhibitory motifs in order to switch off specifi c cell functions. DMB molecules (as previously shown in C4d molecules) do not present species-specific motifs in common chimpanzee, suggesti ng that this species is very close to gorilla or man, also, DMB, like C4d molecules, do not show a trans-species evolution pattern, suggesti ng the existence of extensive homogenization of ;DMB genes within each species or a recent generation of alleles. Finally, a clade grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (a s for C4d nees); this is in contrast to others' results that obtain a human/chimpanzee clade using different DNA sequences.