Autoreactive T cells to topoisomerase I in monozygotic twins discordant for systemic sclerosis

Arthritis Rheum. 2001 Jul;44(7):1654-9. doi: 10.1002/1529-0131(200107)44:7<1654::AID-ART288>3.0.CO;2-O.


Objective: To examine T and B cell responses to topoisomerase I (topo I) in a monozygotic twin pair discordant for systemic sclerosis (SSc).

Methods: The peripheral blood T cell proliferative responses induced by topo I and in vitro anti-topo I antibody production in cultures of T and B cells were examined in an SSc patient with serum anti-topo I antibody and in her healthy monozygotic twin. Topo I-reactive T cell lines were generated from the twin pair and analyzed for antigenic specificity, major histocompatibility complex class II restriction, and T cell receptor (TCR) gene usage.

Results: T cell proliferative responses to topo I were detected in both the SSc patient and her healthy twin, although the kinetics of the T cell response were accelerated in the patient compared with the healthy twin. The estimated frequency of circulating topo I-reactive T cells was 1/6,700 in the SSc patient and 1/39,000 in the healthy twin. Anti-topo I antibody production was observed in cultures of T and B cells from the SSc patient, but not in those from the healthy twin. When the cells from the twins were mixed in different combinations, T cells from the healthy twin did stimulate the SSc patient's B cells to produce anti-topo I antibody through a CD40-dependent mechanism. Topo I-reactive T cell lines generated from the twins had similar characteristics, including a CD4+ phenotype, restriction by HLA-DR, recognition of epitopes within amino acid residues 209-386 of topo I, and dominant usage of the TCR Vbeta20 gene segment.

Conclusion: These results indicate that topo I-reactive T cells were activated and clonally expanded in the SSc patient. However, there were no substantial differences in either phenotypic or functional properties of topo I-reactive T cells obtained from the SSc patient and those obtained from her healthy identical twin. It is likely, therefore, that the anti-topo I antibody response in the SSc patient is induced by in vivo activation of topo I-reactive T cells derived from the normal T cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Twin Study

MeSH terms

  • Aged
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology
  • Cell Division / immunology
  • DNA Fingerprinting
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / immunology
  • DNA Topoisomerases, Type I / metabolism*
  • Female
  • HLA-DQ Antigens / immunology
  • HLA-DR Antigens / immunology
  • Humans
  • Immunologic Memory
  • Kinetics
  • Phenotype
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • Twins, Monozygotic


  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • DNA Topoisomerases, Type I