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.
Albani
S
S
University of California San Diego, Department of Medicine, Institute of Aging, La Jolla 92037.
Roudier
J
J
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D015804:HLA-DR4 Antigen; D010455:Peptides