TY - JOUR
T1 - Adaptable TCR avidity thresholds for negative selection
AU - Stojakovic, Milica
AU - Salazar-Fontana, Laura I.
AU - Tatari-Calderone, Zohreh
AU - Badovinac, Vladimir P.
AU - Santori, Fabio R.
AU - Kovalovsky, Damian
AU - Sant'Angelo, Derek
AU - Harty, John T.
AU - Vukmanovic, Stanislav
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.181.10.6770
DO - 10.4049/jimmunol.181.10.6770
M3 - Article
C2 - 18981094
AN - SCOPUS:58149180575
VL - 181
SP - 6770
EP - 6778
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -