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Optimal T-cell receptor affinity for inducing autoimmunity.

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.

SUBMITTER: Koehli S

PROVIDER: S-EPMC4260541 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Optimal T-cell receptor affinity for inducing autoimmunity.

Koehli Sabrina S Naeher Dieter D Galati-Fournier Virginie V Zehn Dietmar D Palmer Ed E

Proceedings of the National Academy of Sciences of the United States of America 20141119 48

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 ...[more]

PMID: 25411315

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