Association of MHC and rheumatoid arthritis. Association of RA with HLA-DR4: the role of repertoire selection.

Abstract

Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. These alleles share a common amino acid motif in their third hypervariable regions: the shared epitope. In normals and patients with RA, HLA-DR genes exert a major influence on the CD4 alpha beta T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 alpha beta T-cells. However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 alpha beta T-cell repertoire in RA patients. Shared epitope positive HLA-DR alleles may shape the T-cell repertoire by presenting self peptides to CD4 T cells in the thymus. Peptides processed from HLA-DR molecules and encompassing the shared epitope may also be presented by HLA-DQ and select CD4 alpha beta T cells in the thymus. Thus, shared epitope-positive alleles impose a frame on the T-cell repertoire. This predisposing frame is further modified (by unknown factors) to obtain the contracted rheumatoid repertoire.

• Authors: J Roudier
• Journal: Arthritis research (Arthritis Res) Vol. 2 Issue 3 Pg. 217-20 ( 2000) ISSN: 1465-9905 [Print] England
• PMID: 11094433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• HLA-DR4 Antigen

Topics

• Arthritis, Rheumatoid (immunology)
• HLA-DR4 Antigen (immunology)
• Humans
• T-Lymphocytes (immunology)