Epitope-dependent inhibition of T cell activation by the Ea transgene: an explanation for transgene-mediated protection from murine lupus.
J Immunol
; 173(4): 2842-8, 2004 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-15295003
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T
/
Antígenos de Histocompatibilidade Classe II
/
Epitopos de Linfócito T
/
Lúpus Eritematoso Sistêmico
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
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