MHC class II DR classification based on antigen-binding groove natural selection.
Major histocompatibility complex (MHC) genes are highly polymorphic and play key roles in immune susceptibility and resistance to pathogens. While the immunological and structural functions of several human and murine alleles have been analyzed, little is known about the MHC molecules of other animals. Here, we could classify five mammalian species into three groups (human, cow and dog, and cat and pig) on the basis of DRB nucleotide sequences, synonymous and nonsynonymous mutation rates, and natural selection of individual residues. These observations, along with the locations of the positively and negatively selected residues in three-dimensional DR structures, suggest that the antigen-recognition sites of swine and feline DR molecules have been negatively selected while those of bovine and canine DR molecules have been positively selected. Human DR molecules show evidence of high negative and positive selection. Our observations suggest that MHC-DR molecules are under different selective force depending on each species.
Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan.
Shin-nosuke
SN
Takeshima
Akinori
A
Sarai
Yoshinori
Y
Sarai
Naruya
N
Saitou
Yoko
Y
Aida
D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002415:Cats; D002417:Cattle; D004285:Dogs; D006684:HLA-DR Antigens / Q000737:chemistry / Q000145:classification* / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000145:classification* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D012641:Selection, Genetic; D013552:Swine / Q000235:genetics / Q000276:immunology
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II