Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: Possible implications for the generation of HLA polymorphism

J. A. Lopez de Castro, J. L. Strominger, D. M. Strong, H. T. Orr

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67 Scopus citations

Abstract

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 in 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-A2 and HLA-A28 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.

Original languageEnglish (US)
Pages (from-to)3813-3817
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number12 I
DOIs
StatePublished - 1982

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