CDR3 sequence motifs shared by oligoclonal rheumatoid arthritis synovial T cells. Evidence for an antigen-driven response. uri icon

Overview

abstract

  • T lymphocytes reactive with as yet undefined joint-localized foreign or autoantigens may be important in the pathogenesis of RA. Molecular studies demonstrating skewed T cell antigen receptor (TCR) variable gene usage and selective expansion of particular T cell clones within the synovial compartment support this view. Based on our recent study documenting selective expansion of V beta 17+ T cells in RA, we have pursued the identification of T cells relevant to the disease process, in an informative patient, by combining molecular analysis of freshly explanted RA synovial tissue V beta 17 TCR transcripts with in vitro expansion of V beta 17+ synovial tissue T cell clones. Peripheral blood V beta 17 cDNA transcripts proved heterogeneous. In contrast, two closely related sequences, not found in the peripheral blood, dominated synovial tissue V beta 17 transcripts, suggesting selective localization and oligoclonal expansion at the site of pathology. CD4+, V beta 17+ synovial tissue-derived T cell clones, isolated and grown in vitro, were found to express TCR beta chain transcripts homologous to the dominant V beta 17 synovial tissue sequences. One clone shares with a dominant synovial tissue sequence a conserved cluster of 4/5 amino acids (IGQ-N) in the highly diverse antigen binding CDR3 region, suggesting that the T cells from which these transcripts derive may recognize the same antigen. These findings have permitted a complete characterization of the alpha/beta TCR expressed by putatively pathogenic T cell clones in RA. Functional analysis suggests that the conserved CDR3 sequence may confer specificity for, or restriction by, the MHC class II antigen, DR4.

publication date

  • December 1, 1994

Research

keywords

  • Arthritis, Rheumatoid
  • Receptors, Antigen, T-Cell, alpha-beta
  • Synovial Membrane
  • T-Lymphocyte Subsets

Identity

PubMed Central ID

  • PMC330088

Scopus Document Identifier

  • 0028007176

Digital Object Identifier (DOI)

  • 10.1172/JCI117624

PubMed ID

  • 7989613

Additional Document Info

volume

  • 94

issue

  • 6