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 leader peptide, but not in the transmembrane segment. An analysis of the residues critical in the conformation of the Mhc-DR peptide-binding site was done in order to look for a Mhc-DR homologue site; synonymous substitutions are favoured in this homologous HLA-DM region. This is another finding that supports the possibility that DM could not be typically presenting molecules. The immunoreceptor inhibition motif Tyr 230-Thr/Ser 231-Pro 232-Leu 233 (ITIM) is invariantly present in apes for at least 15 million years, and may have a double function: 1) To direct 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 unnecessary HLA-DR molecules, once all available antigenic peptides are loaded. Other molecules, like NK-cell receptors and Fc receptors, bear this type of tyrosine-based inhibitory motifs in order to switch off specific cell functions. DMB molecules (as previously shown in C4d molecules) do not present species-specific motifs in common chimpanzee, suggesting that this species is very close to gorilla or man; also, DMB, like C4d molecules, do not show a trans-species evolution pattern, suggesting 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 (as for C4d trees); this is in contrast to others' results that obtain a human/chimpanzee clade using different DNA sequences.
Alvarez
M
M
Department of Immunology, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
Recio
M J
MJ
Martinez-Laso
J
J
Pérez-Blas
M
M
Garcia-de-la-Torre
C
C
Vargas-Alarcón
G
G
Alegre
R
R
Gomez-Casado
E
E
Arnaiz-Villena
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D005802:Genes, MHC Class II; D014644:Genetic Variation; D006071:Gorilla gorilla; D006681:HLA-D Antigens / Q000737:chemistry / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D019974:Pan paniscus; D002679:Pan troglodytes; D011148:Pongo pygmaeus; D011323:Primates / Q000235:genetics* / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D014443:Tyrosine