High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen-driven immune responses

Arthritis Rheum. 1996 Mar;39(3):446-53. doi: 10.1002/art.1780390312.

Abstract

Objective: To investigate T cell antigen receptor (TCR) clonotypes in rheumatoid arthritis (RA) lesions.

Methods: Reverse transcriptase-polymerase chain reaction with TCR V beta family-specific primers and subsequent single-strand conformation polymorphism (SSCP) analysis were performed. Direct nucleotide sequencing was also conducted.

Results: A distinct clonal expansion of T cells was observed in the synovium. Furthermore, identical bands in samples of different areas of the same lesion were obtained by SSCP analysis. Nucleotide sequencing revealed that T cell clonotypes of identical mobility on SSCP analysis had the same nucleotide sequence and thus were identical clones. In 6 RA patients, 60-100% of the expanded T cell clonotypes had identical migration patterns in 2 different samples, indicating that this percentage represents commonly existing T cell clonotypes in the affected joint. Furthermore, the J beta 2.1 gene segment was used predominantly by the TCR V beta clonotypes that commonly expanded in the different portions of the same joint.

Conclusion: These results suggest that the immune response in RA is not random, but rather is driven by common stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Clone Cells
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Testing
  • Humans
  • Immunoglobulin Variable Region / immunology
  • Immunophenotyping
  • Middle Aged
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Sequence Analysis, DNA
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / ultrastructure

Substances

  • Histocompatibility Antigens Class II
  • Immunoglobulin Variable Region
  • Receptors, Antigen, T-Cell