- Paper Report
- Open Access
Does elevated DR on RA B cells reveal cryptic epitopes?
- Robert Busch1
© Biomed Central Ltd 2001
- Received: 7 August 2001
- Accepted: 3 September 2001
- Published: 4 September 2001
- Allele specific monoclonal antibodies
- antigen presentation
- MHC class II
Human leukocyte antigen (HLA)- DR molecules present antigens to CD4+ T cells. DR alleles sharing a common polymorphism at residues 67-74 of the DR? chain confer susceptibility to severe rheumatoid arthritis (RA). However, the biological role of HLA-DR remains poorly understood. The authors previously reported that expression of HLA-DM, a catalyst of DR/peptide binding, is decreased in B cells of RA patients, suggesting a role for antigen presentation defects (see Additional information). The aims of this study were to quantify DR expression in RA and to examine consequences of quantitative differences in DR levels for T-cell responses.
RA-associated DR4 molecules were elevated twofold to threefold on RA patients' (n = 6) B cells compared to controls (n = 5). This was true for RA-associated DR4 variants such as DR0401, for nonassociated DR variants such as DR0402, and for the nonassociated DR11 allele. Upregulation was less for other DR alleles, such as DR1 (weakly RA-associated) and DR7 (nonassociated), and for DR molecules containing an alternate ? chain (DR53). Levels of DR15 molecules were reduced in RA. No correlation with B-cell activation, disease activity, or use of anti-inflammatory drugs was observed. Increased DR1 levels on transfected fibroblasts resulted in improved presentation of antigenic peptides to T cells and in improved responsiveness to mutated peptides. The authors concluded that elevated DR levels during RA could cause presentation of normally cryptic self peptides to T cells.
Quantitative flow cytometry, cytotoxicity assay, transfection
Louis-Plence P, Kerlan-Candon S, Morel J, Combe B, Clot J, Pinet V, Eliaou JF: The down-regulation of HLA-DM gene expression in rheumatoid arthritis is not related to their promoter polymorphism. J Immunol 2000, 165:4861-4869 (PubMed abstract).