| First Author | Martinez-Soría E | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 4 | Pages | 2842-8 |
| PubMed ID | 15295003 | Mgi Jnum | J:92656 |
| Mgi Id | MGI:3054270 | Doi | 10.4049/jimmunol.173.4.2842 |
| Citation | Martinez-Soria E, et al. (2004) 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 |
| abstractText | 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. |
