Identification of the DRw10 DRβ₁-chain allele as encoding a polymorphic class II major histocompatibility complex epitope otherwise restricted to DRβ₂ molecules of the DRw53 type

Although the polymorphic human Ia epitope recognized by monoclonal antibody 109d6 typically is expressed by DRw53β₂ chains, the epitope was shown to be encoded by distinctive DRβ₁ chains of a DRw10 haplotype in three unrelated DR4-negative individuals with rheumatoid arthritis. No evidence of a DRβ₂ (DRβ4) chain molecule was found to be encoded by this haplotype. Using two-dimensional gel analysis and partial radioactive N-terminal microsequencing, the DR and DQ products were characterized in the heterozygous members of a family in which the segregation of both varieties of DRβ chains specifying the 109d6 epitope was demonstrated. The expression of the epitope on the DRβ₂ chain, but not on the DRβ₁ chain, was abolished by preventing N-linked glycosylation, although in both molecules the epitope was not altered by neuraminidase digestion. The potential structural bases of the serologic cross reactions of DRw10 are discussed, as are the possible implications of the findings for the definition of susceptibility to rheumatoid arthritis.