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 journalArticle

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
Publication statusPublished - 15 Nov 2008
Externally publishedYes

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T-Lymphocytes
Transgenic Mice
Central Tolerance
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Autoimmune Diseases
Peptides
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Stojakovic, M., Salazar-Fontana, L. I., Tatari Calderone, Z., Badovinac, V. P., Santori, F. R., Kovalovsky, D., ... Vukmanovic, S. (2008). Adaptable TCR avidity thresholds for negative selection. Journal of Immunology, 181(10), 6770-6778.

Adaptable TCR avidity thresholds for negative selection. / 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.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 6770-6778.

Research output: Contribution to journalArticle

Stojakovic, M, Salazar-Fontana, LI, Tatari Calderone, Z, Badovinac, VP, Santori, FR, Kovalovsky, D, Sant'Angelo, D, Harty, JT & Vukmanovic, S 2008, 'Adaptable TCR avidity thresholds for negative selection', Journal of Immunology, vol. 181, no. 10, pp. 6770-6778.
Stojakovic M, Salazar-Fontana LI, Tatari Calderone Z, Badovinac VP, Santori FR, Kovalovsky D et al. Adaptable TCR avidity thresholds for negative selection. Journal of Immunology. 2008 Nov 15;181(10):6770-6778.
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. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 6770-6778.
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