MOLECULAR-BASIS FOR THE ASSOCIATION BETWEEN HLA DR4 AND RHEUMATOID-ARTHRITIS - FROM THE SHARED EPITOPE HYPOTHESIS TO A PEPTIDIC MODEL OF RHEUMATOID-ARTHRITIS

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.