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cDNA clones representing products of the DR7 and DRw53 beta-chain genes were isolated from the human B-lymphoblastoid cell line MANN (DR7,DRw53,DQw2, DPw2). The DRw53 beta sequence was identical to a DRw53 beta sequence derived from cells with a DR4 haplotype. In contrast, the DR7 beta sequence was as unrelated to DR4 beta sequence as it was to other DR beta-related genes, except at the 3'-untranslated region. These results suggest that the DR7 and DR4 haplotypes may have been derived relatively recently from a common ancestral haplotype and that the DR4 and DR7 beta-chain genes have undergone more rapid diversification in their beta 1 domains, most probably as a result of natural selection, than have the DRw53 beta-chain genes. Short tracts of sequence within the DR7 and DRw53 beta 1 domains were shared with other DR beta sequences, indicating that exchanges of genetic information between beta 1 domains of DR beta-related genes have played a part in their evolution. Serological analysis of mouse L-cell transfectants expressing surface HLA-DR7 molecules, confirmed by antibody binding and allelic sequence comparisons, identified amino acid residues that may be critical to the binding of a monomorphic DR- and DP-specific monoclonal antibody.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

07/1987

Volume

84

Pages

4929 - 4933

Keywords

Amino Acid Sequence, Animals, B-Lymphocytes, Base Sequence, Cell Line, DNA, Gene Conversion, Genes, Genes, MHC Class II, HLA-D Antigens, HLA-DR Antigens, HLA-DR7 Antigen, HLA-DRB4 Chains, Humans, L Cells (Cell Line), Mice, Polymorphism, Genetic