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

Martinez-Soria, Eduardo
Iwamoto, Masahiro
Kosco-Vilbois, Marie
Published in Journal of Immunology. 2004, vol. 173, no. 4, p. 2842-2848
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 AnimalsAntigen Presentation/immunologyB-Lymphocytes/immunologyDisease Models, AnimalEpitopes, T-Lymphocyte/*immunologyFlow CytometryHistocompatibility Antigens Class II/*genetics/immunologyLupus Erythematosus, Systemic/immunology/*prevention & controlLymphocyte Activation/*immunologyMiceT-Lymphocytes/*immunologyTransgenes
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Other version: http://www.jimmunol.org/cgi/reprint/173/4/2842.pdf
PMID: 15295003
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