Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism.
The primary structure of two highly crossreactive human histocompatibility antigens, HLA-A28 and HLA-A2, has been determined to 96% and 90%, respectively, of the papain-solubilized molecules. Their sequences have been compared with the sequence of HLA-B7 and with each other in order to outline the sites of diversity. The overall homology between HLA-B7 and these HLA-A antigens is 86%. A large majority of the differences are located between residues 43 and 195. Within this area, substitutions cluster in at least three segments--residues 65-80, 105-116, and 177-194. HLA-A28 and HLA-A2 show 96% homology. Most of the differences fall within segments 65-74 and 107-116. These results strongly support the suggestion that residues in these segments are integral parts of the alloantigenic determinants of HLA-A28 and HLA-A2. It is further proposed that these three clusters may constitute major, albeit not exclusive, sites of antigenic diversity in human histocompatibility antigens. The nature of the differences among HLA-B7, HLA-A28, and HLA-A2 in the first variable segment suggests that gene conversion might play some role in the generation of HLA polymorphism.
D000595:Amino Acid Sequence; D005075:Biological Evolution; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes; D005785:Gene Conversion; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007128:Immunoglobulin Fragments; D046911:Macromolecular Substances; D011110:Polymorphism, Genetic
D000939:Epitopes; D006680:HLA Antigens; D007128:Immunoglobulin Fragments; D046911:Macromolecular Substances