Genetic susceptibility to rheumatoid arthritis and human leukocyte antigen class II polymorphism. The role of shared conformational determinants

Am J Med. 1988 Dec 23;85(6A):17-9. doi: 10.1016/0002-9343(88)90374-9.


Genetic susceptibility for rheumatoid arthritis has been associated with both human leukocyte antigen (HLA)-DR4 and HLA-DR1, depending on the ethnic origin of the population under study. Furthermore, various subtypes of DR4 exist, only some of which appear to be associated with rheumatoid arthritis. DNA sequence analysis of the DR-beta chain genes encoding the DR4 subtypes as well as DR1 has led to the observation that similar third hypervariable region sequences are found on rheumatoid arthritis-associated DR-beta chain alleles. The data indicate that third hypervariable region sequence polymorphisms strongly influence T cell recognition as well as risk for rheumatoid arthritis. This has led to the hypothesis that genetic susceptibility for rheumatoid arthritis is due to a group of similar third hypervariable region sequences that may share conformational determinants important in antigen presentation and/or immune regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alleles
  • Amino Acids / analysis
  • Arthritis, Rheumatoid / genetics*
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / genetics*
  • Haplotypes
  • Humans
  • Polymorphism, Genetic*
  • Receptors, Antigen, T-Cell / genetics


  • Amino Acids
  • HLA-DR Antigens
  • Receptors, Antigen, T-Cell