Molecular characterization by high-resolution isoelectric focusing of the products encoded by the class II region loci of the major histocompatibility complex in humans. I. DR and DQ gene variants

Abstract

We describe a new approach to the analysis of the structural polymorphism of the DRβ, DQα, and DQβ polypeptide chains of human histocompatibility class II antigens. In comparison to conventional two-dimensional gel studies, this method provides sharper definition of the protein bands and side-by-side comparisons within the same gel, thereby permitting the detection of minor differences in the isoelectric points of the protein chains. Using this methodology we have analyzed the IEF polymorphism and the variability in the number of the DRβ chains encoded by different DR haplotypes. Twenty DRβ chain variants, which include the products of no less than two separate DRβ loci, have been thus far identified. Alleles at one of these loci are assumed to code for DRβ chains carrying the DR alloespecificities DR1, DR2, DR3, DR4, DR5, DRw6, DR7, and DR8. Alleles at a second DRβ locus encode DRβ chains that may be shared by serologically DR-different haplotypes and carry supertypic serologic specificities (i.e., DRw52 and DRw53). We also demonstrate here that the structural polymorphisms of the DQα and DQβ chains are more extensive than previously thought, report the characterization of 14 DQβ variants, and define their relationship to the previously described DQw serologic specificities. In addition, we describe the class II haplotype associations observed for the different DR and DQ variants characterized.