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

Martinez-Soria, Eduardo; Ibnou-Zekri, Nabila; Iwamoto, Masahiro; Santiago-Raber, Marie-Laure; Kikuchi, Shuichi; Kosco-Vilbois, Marie; Izui, Shozo

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Title		Epitope-dependent inhibition of T cell activation by the Ea transgene: an explanation for transgene-mediated protection from murine lupus
Authors		Martinez-Soria, Eduardo Ibnou-Zekri, Nabila Iwamoto, Masahiro Santiago-Raber, Marie-Laure Kikuchi, Shuichi Kosco-Vilbois, Marie Izui, Shozo
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		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
Identifiers		DOI: 10.4049/jimmunol.173.4.2842 PMID: 15295003
Full text		Article - Limited access to UNIGE Other version: http://www.jimmunol.org/cgi/reprint/173/4/2842.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
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: Journal of Immunology, 2004, vol. 173, n° 4, p. 2842-2848. https://archive-ouverte.unige.ch/unige:11443