Full-length DQβ cDNA sequences of HLA-DR2/DQw1 subtypes: Genetic interactions between two DQβ loci generate human class II HLA diversity

Abstract

Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one αβ heterodimer of DQ molecule is expressed by each subtype and the DQB chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQβ cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQβ chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10–17 amino acids in the first domain and by 3–7 residues in the C-terminal sequence. Comparison among the available DQβ sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2, Dw2, DQw1 and DR3, DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 β alleles and (2) an evolutionary scheme may be proposed to relate the various β alleles of the four major DQ specificities.