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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 (US)
Pages (from-to)6770-6778
Number of pages9
JournalJournal of Immunology
Volume181
Issue number10
DOIs
StatePublished - Nov 15 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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