Polymorphism of Mhc-DRB alleles in Cercopithecus aethiops (green monkey): generation and functionality.
DRB genes have been studied for the first time in green monkeys (Cercopithecus aethiops). Eleven new DRB alleles (exon 2, exon 3) have been obtained and sequenced from cDNA. A limited number of lineages have been identified: DRB1*03 (4 alleles), DRB1*07 (3 alleles), DRB5 (1 allele), DRB*w6 (1 allele), and DRB*w7 (2 alleles). The existence of Ceae-DRB1 duplications is supported by the finding of 3 DRB1 alleles in 3 different individuals. Ceae-DRB1*0701 may be non-functional because it bears serine at position 82, which hinders molecule surface expression in mice; the allele is only found in Ceae-DRB duplicated haplotypes. Base changes in cDNA Ceae-DRB alleles are consistent with the generation of polymorphism by point mutations or short segment exchanges between alleles. The eleven green monkey DRB alleles meet the requirements for functionality as antigen-presenting molecules (perhaps, excluding DRB1*0701), since: 1) they have been isolated from cDNA and do not present deletions, insertions or stop codons: 2) structural motifs necessary for a correct folding of the molecule, for the formation of DR/DR dimers and for CD4 interactions are conserved, and 3) the number of non-synonymous substitutions is higher than the number of synonymous substitutions in the peptide binding region (PBR), while the contrary holds true for the non-PBR region.
Department of Immunology, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
M
M
Rosal-Sánchez
E
E
Paz-Artal
M A
MA
Moreno-Pelayo
N
N
Martínez-Quiles
J
J
Martínez-Laso
J M
JM
Martín-Villa
A
A
Arnaiz-Villena
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D018076:DNA, Complementary; D019143:Evolution, Molecular; D006649:Histocompatibility Antigens / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D018076:DNA, Complementary; D006649:Histocompatibility Antigens