Identification and characterization of SmD183-119-reactive T cells that provide T cell help for pathogenic anti-double-stranded DNA antibodies

Arthritis Rheum. 2003 Feb;48(2):475-85. doi: 10.1002/art.10762.


Objective: The C-terminal peptide of amino acids 83-119 of the SmD1 protein is a target of the autoimmune response in human and murine lupus. This study was undertaken to test the hypothesis that SmD1(83-119)-reactive T cells play a crucial role in the generation of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies.

Methods: Splenic or lymph node T cells derived from unmanipulated as well as SmD1(83-119)-immunized NZB/NZW mice were analyzed in vitro by enzyme-linked immunospot (ELISpot) assay to determine T cell help for anti-dsDNA generation induced by the SmD1(83-119) peptide. Cytokines expressed by these T cells were measured by ELISpot assay, enzyme-linked immunosorbent assay, and flow cytometry. SmD1(83-119)- and ovalbumin-specific T cell lines were generated and characterized.

Results: The SmD1(83-119) peptide, but not the control peptides, significantly increased the in vitro generation of anti-dsDNA antibodies in cultures from unmanipulated NZB/NZW mice. Interferon-gamma (IFNgamma), interleukin-2 (IL-2), IL-4, transforming growth factor beta, and IL-10 production increased in response to the peptide in young mice; only IFNgamma and IL-2 were increased in older, diseased mice. Activation of SmD1(83-119)-reactive T cells by immunization of NZB/NZW mice resulted in elevated anti-dsDNA synthesis and, later, increased antibodies to SmD1(83-119). Most cells in SmD1(83-119)-specific CD4+ T cell lines helping both antibodies had increased intracellular expression of IFNgamma, and most expressed both IFNgamma and IL-4.

Conclusion: The SmD1(83-119) peptide plays an important role in generating T cell help for autoantibodies, including anti-dsDNA, and activates different subsets of T cells as defined by distinct cytokine expression. This peptide is an interesting target structure for the modulation of autoreactive T cells, and its characterization may contribute to our understanding of the role of autoantigen-reactive T cells in the pathogenesis of SLE.

Publication types

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

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Autoantigens
  • B-Lymphocytes / immunology
  • Cell Line
  • Cytokines / analysis
  • DNA / immunology*
  • Female
  • Flow Cytometry
  • Immunization
  • In Vitro Techniques
  • Mice
  • Mice, Inbred NZB
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology
  • Plasma Cells / immunology
  • Ribonucleoproteins, Small Nuclear / immunology*
  • Ribonucleoproteins, Small Nuclear / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • snRNP Core Proteins


  • Autoantibodies
  • Autoantigens
  • Cytokines
  • Peptide Fragments
  • Ribonucleoproteins, Small Nuclear
  • SNRPD1 protein, human
  • snRNP Core Proteins
  • DNA