Autoreactive responses to an environmental factor. 2. Phthalate-induced anti-DNA specificity is downregulated by autoreactive cytotoxic T cells

Immunology. 2004 May;112(1):94-104. doi: 10.1111/j.1365-2567.2004.01842.x.


An environmental factor (phthalate) was shown, in our previous study, to induce serum anti-DNA responses in BALB/c, NZB and lupus-prone NZB/W F1 mice. Out of such anti-phthalate responses, cross-reactive populations were identified that strongly bind phthalate, DNA, or both. A phthalate-specific BALB/c monoclonal antibody, 2C3-Ig (gamma1,kappa), showed considerable affinity for DNA and had extensive sequence homology with the heavy and light chain variable regions of a known anti-DNA immunoglobulin, BV04-01, from lupus-prone NZB/W F1 mice. This study was initiated to address how BALB/c mice, but not NZB/W F1 mice, are protected from these adverse autoreactive B cells. Using 2C3 hybridoma cells as the prototype autoreactive BALB/c B cell, we determined whether its DNA-binding monoclonal antibody would induce any regulatory cell-mediated immune responses. Synthetic idiopeptides corresponding to the heavy and light chain variable regions of 2C3-Ig were found to be effective at inducing specific effector cells in BALB/c mice, but not in lupus-prone F1 mice. The splenocytes from BALB/c mice incubated in vitro with the idiopeptides, particularly the complementarity-determining region 1 (VL1) of the 2C3-Ig light chain, showed significant proliferative and cytolytic responses. A CD8+ cytotoxic T-lymphocyte (CTL) response was elicited that recognized the VL1 peptide presented by the Kd allele, and affected the growth of 2C3 cells. In vivo depletion of CD8+ T cells in BALB/c mice significantly decreased this CTL activity but increased the anti-DNA humoral response. These results suggest that autoreactive CTLs are induced in non-autoimmune prone mice as a mechanism to downregulate self-reactive B cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibody Specificity
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division / immunology
  • Cells, Cultured
  • Complementarity Determining Regions / immunology
  • Cytotoxicity, Immunologic
  • DNA / immunology*
  • Female
  • Hemocyanins / immunology
  • Histocompatibility Antigens Class I / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NZB
  • Molecular Sequence Data
  • Phthalic Acids / immunology*


  • Antibodies, Antinuclear
  • Complementarity Determining Regions
  • Histocompatibility Antigens Class I
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Phthalic Acids
  • phthalic acid
  • DNA
  • Hemocyanins
  • keyhole-limpet hemocyanin