Adaptable TCR avidity thresholds for negative selection

Milica Stojakovic, Laura I. Salazar-Fontana, Zohreh Tatari-Calderone, Vladimir P. Badovinac, Fabio R. Santori, Damian Kovalovsky, Derek Sant'Angelo, John T. Harty, Stanislav Vukmanovic

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8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6770-6778
Number of pages9
JournalJournal of Immunology
Volume181
Issue number10
DOIs
Publication statusPublished - 15 Nov 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Stojakovic, M., Salazar-Fontana, L. I., Tatari-Calderone, Z., Badovinac, V. P., Santori, F. R., Kovalovsky, D., Sant'Angelo, D., Harty, J. T., & Vukmanovic, S. (2008). Adaptable TCR avidity thresholds for negative selection. Journal of Immunology, 181(10), 6770-6778. https://doi.org/10.4049/jimmunol.181.10.6770