Association of MHC and rheumatoid arthritis: Association of RA with HLA-DR4 - the role of repertoire selection
AUTOR(ES)
Roudier, Jean
FONTE
BioMed Central
RESUMO
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 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 αβ 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 αβ 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 αβ 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=130006Documentos Relacionados
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