A novel association of DQα and DQβ genes in the DRw10 haplotype. Determination of a DQw1 specificity by the DQ β-chain

The association of the class II genes of the DRw10 haplotype from a cell line, NASC, initiated from a member of a well characterized family, was analyzed by sequencing cDNA clones corresponding to DRβ1, DQα, and DQβ genes. An identical haplotype was also identified in the Raji cell line. In addition to typing as DRw10 and DQw1 with HLA typing sera both, the NASC and Raji cell lines were shown to react strongly with the monoclonal antibodies 109d6 (specific for DRw10β1 and DRw53β2 gene products) and Genox 3.5.3 (specific for DQw1) and exhibited the restriction fragment length polymorphism indicative of a DRw10, DQw1 haplotype. The DRβ1 gene corresponding to the DRw10 specificity was found to have a first domain sequence different from all other DRβ1 genes. Sequence analysis of the 3'-untranslated region of this DR β-chain gene showed a significant divergence from the 3' untranslated region of the DRw53 family of haplotypes and a lesser divergence from that of the DRw52 and DR1/DR2 families. The sequence of the DQβ genes corresponding to the DQw1 specificity in the DRw10 haplotype was found to be identical to the DQβ gene from a DR1, DQw1 haplotype. Surprisingly, however, the DQα gene did not resemble other DQw1-like DQα genes, but was identical in sequence to the DQα gene found in DR4 haplotypes. The novel association of DQα and DQβ genes in the DRw10 haplotype revealed in these studies may result from a double recombinational event. More consequentially, these studies strongly suggest that the DQw1 specificity recognized by Genox 3.5.3 is determined by the DQβ chain and is not affected by the DQ α-chain.