Molecular basis for the association between HLA DR4 and rheumatoid arthritis. From the shared epitope hypothesis to a peptidic model of rheumatoid arthritis

Clin Biochem. 1992 Jun;25(3):209-12. doi: 10.1016/0009-9120(92)90328-p.


Susceptibility to rheumatoid arthritis (RA) maps to residues QKRAA/QRRAA in the third hypervariable region of the HLA DR beta 1 chain. Peptides from the same area of MHC class II molecules are able to modulate the T-cell repertoire by deleting self-reactive T-cells. The Epstein Barr virus glycoprotein gp110 and the dna J heat-shock protein from E. coli mimic the third hypervariable region of HLA-Dw4DR beta 1. Thus, the same area of HLA DR beta 1 carries susceptibility to RA, modulates the T-cell repertoire and is mimicked by human pathogens. RA may originate from a particular shape imposed on the T-cell repertoire by the QKRAA/QRRAA sequence in the third hypervariable region of HLA DR beta 1.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Arthritis, Rheumatoid / immunology*
  • Epitopes / immunology
  • HLA-DR4 Antigen / immunology*
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Peptides / immunology
  • T-Lymphocytes / immunology


  • Epitopes
  • HLA-DR4 Antigen
  • Peptides