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Scientific article
English

Epitope-dependent inhibition of T cell activation by the Ea transgene: an explanation for transgene-mediated protection from murine lupus

Published inThe Journal of immunology, vol. 173, no. 4, p. 2842-2848
Publication date2004
Abstract

A high level expression of the Ea(d) transgene encoding the I-E alpha-chain is highly effective in the suppression of lupus autoantibody production in mice. To explore the possible modulation of the Ag-presenting capacity of B cells as a result of the transgene expression, we assessed the ability of the transgenic B cells to activate Ag-specific T cells in vitro. By using four different model Ag-MHC class II combinations, this analysis revealed that a high transgene expression in B cells markedly inhibits the activation of T cells in an epitope-dependent manner, without modulation of the I-E expression. The transgene-mediated suppression of T cell responses is likely to be related to the relative affinity of peptides derived from transgenic I-E alpha-chains (Ealpha peptides) vs antigenic peptides to individual class II molecules. Our results support a model of autoimmunity prevention based on competition for Ag presentation, in which the generation of large amounts of Ealpha peptides with high affinity to I-A molecules decreases the use of I-A for presentation of pathogenic self-peptides by B cells, thereby preventing excessive activation of autoreactive T and B cells.

Keywords
  • Animals
  • Antigen Presentation/immunology
  • B-Lymphocytes/immunology
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte/*immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class II/*genetics/immunology
  • Lupus Erythematosus, Systemic/immunology/*prevention & control
  • Lymphocyte Activation/*immunology
  • Mice
  • T-Lymphocytes/*immunology
  • Transgenes
Citation (ISO format)
MARTINEZ-SORIA, Eduardo et al. Epitope-dependent inhibition of T cell activation by the Ea transgene: an explanation for transgene-mediated protection from murine lupus. In: The Journal of immunology, 2004, vol. 173, n° 4, p. 2842–2848. doi: 10.4049/jimmunol.173.4.2842
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ISSN of the journal0022-1767
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