Class ii major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DRβ1 genes in two DR1, DRw10–positive individuals specify the same inferred amino acid sequence as the DRβ1 and DRβ2 Genes of a DR4 (Dw14) haplotype

Abstract

The DR1 and DRw10β₁, chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class II major histocompatibility complex specificities. The sequences of the DR1β₁ chains from both patients were identical, differing from previously reported DRβ₁ chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val‐Ala) and 86 (Gly‐Val), and by a silent mutation at the last nucleotide of codon 78 (C–T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRw10β₁, chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53β₂ chain of the DR4 haplotype. The third diversity regions of the DR1β (amino acids 67–74) and the DRw10β₁ chains (amino acids 67–73) were identical, respectively, with those of the DR4 (Dw14) β₁, and β₂ chains, raising the possibility that in these patients, the third diversity regions of the two DRβ₁, chain genes present in trans are conformationally equivalent to the cis‐encoded third diversity regions of the DR4 (Dw14), DRβ₁, and β₂ chains. The nucleotide sequences of the DQβ complementary DNA clones were identical to that of the DQw1β chain, and no DRβ₂ complementary DNA clones were identified.