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Skewed T-cell receptor BV14 and BV16 expression, and shared complementarity-determining region 3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis
Arthritis Res Thervolume 5, Article number: 123 (2003)
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, in which T cells are thought to play an important role in the rheumatoid synovium. We hypothesized that if the T-cell receptor (TCR) repertoire of infiltrating T cells is shaped by interaction with common self-antigens or microbial antigens in the context of susceptible human leukocyte antigen genes, these synovial T cells may share some TCR structural features in different patients. In this study, synovial lesion tissue, synovial fluid and blood specimens from 37 RA patients and seven control patients were analyzed for TCR repertoire. The results indicated highly skewed BV14 and BV16 in the synovial lesion tissue and BV16 in synovial fluid of RA, while control synovial material had diverse BV distribution. A trend for correlation between the skewed BV16 but not BV14 and the expression of DRB1*0405 was found in this cohort of Chinese RA patients. Immunoscope analysis of the V–D–J region showed oligoclonal expansion of BV14+ and BV16+ T cells in some cases, while polyclonal patterns were frequently seen in other specimens. Refinement of the V–D–J region profile by detailed immunoscope analysis using BV and BJ primers revealed common clonotypes that utilized the same BV14 or BV16 and the same BJ, and had similar complementarity-determining region 3 (CDR3) length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and the CDR3 structural characteristics in synovial infiltrating T cells of RA, and have implications in novel immunotherapy.