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2008:
Stojakovic Milica; Salazar-Fontana Laura I; Tatari-Calderone Zohreh; Badovinac Vladimir P; Santori Fabio R; Kovalovsky Damian; Sant'Angelo Derek; Harty John T; Vukmanovic Stanislav
Adaptable TCR avidity thresholds for negative selection.
Journal of immunology (Baltimore, Md. : 1950) 2008;
181(
10):.
Central tolerance plays a significant role in preventing autoimmune diseases by eliminating T cells with high and intermediate avidity for self. To determine the manner of setting the threshold for deletion, we created a unique transgenic mouse strain with a diverse T cell population and globally increased TCR avidity for self-peptide/MHC complexes. Despite the adaptations aimed at reducing T cell reactivity (reduced TCR levels and increased levels of TCR signaling inhibitor CD5), transgenic mice displayed more severe experimental allergic encephalomyelitis and lupus. The numbers and activity of natural (CD4(+)CD25(+)) regulatory T cells were not altered. These findings demonstrate that the threshold for deletion is adaptable, allowing survival of T cells with higher avidity when TCR avidity is globally increased.
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