Optimal T-cell receptor affinity for inducing autoimmunity

Sabrina Koehli, Dieter Naeher, Virginie Galati-Fournier, Dietmar Zehn, Ed Palmer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

T-cell receptor affinity for self-antigen has an important role in establishing self-tolerance. Three transgenic mouse strains expressing antigens of variable affinity for the OVA transgenic-I T-cell receptor were generated to address how TCR affinity affects the efficiency of negative selection, the ability to prime an autoimmune response, and the elimination of the relevant target cell. Mice expressing antigens with an affinity just above the negative selection threshold exhibited the highest risk of developing experimental autoimmune diabetes. The data demonstrate that close to the affinity threshold for negative selection, sufficient numbers of self-reactive T cells escape deletion and create an increased risk for the development of autoimmunity.

Original languageEnglish
Pages (from-to)17248-17253
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number48
DOIs
StatePublished - 2 Dec 2014
Externally publishedYes

Keywords

  • Affinity
  • Autoimmunity
  • T cell
  • TCR
  • Tolerance

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