HLA-DR2 subtypes form an additional supertypic family of DR beta alleles.

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Abstract
Homozygous lymphoblastoid cell lines representing Dw subtypes of the DR2 serotype were studied for structural polymorphism at DR.beta.. These subtypes included Dw2, Dw12, and non-Dw2/non-Dw12. Analysis two-dimensional gel electrophoresis showed that two DR.beta. genes were expressed in each cell line studied. One of these expressed genes encoded a protein that was nonpolymorphic on two-dimensional gel electrophoresis among all subtypes. The second expressed DR.beta. gene was polymorphic and migrated to a position on two-dimensional gels dependent on the subtype of the cell line. cDNA sequence analysis of the DR.beta. genes revealed a DR.beta. gene identical between the Dw2 and Dw12 subtypes, which correlates with the nonpolymorphic spot on two-dimensional gels. A second gene was sequenced that exhibited variability between the Dw2 and Dw12 subtypes. This variability takes the form of clustered point mutations in the first domain of the molecules. The alleles from the DR.beta. genes of a non-Dw2/non-Dw12 cell line, AZH, were unusual in sequence. In contrast to other DR.beta. alleles, the AZH genes may have been generated by a double recombinational event between two DR.beta. loci from a DR2 parent. The DR2 serotype may also constitute a supertypic "family," with one DR.beta. gene relatively nonpolymorphic, and one that varies with Dw subtype.