Altered differentiation, diminished pathogenicity, and regulatory activity of myelin-specific T cells expressing an enhanced affinity TCR.

ABSTRACT: Whereas increased affinity enhances T cell competitiveness after immunization, the role of affinity in modulating the pathogenicity of self-reactive T cells is less established. To assess this, we generated two myelin-specific, class II MHC-restricted TCR that differ only in a buried hydroxymethyl that forms a common TCR β-chain V region variant. The variation, predicted to increase TCR stability, resulted in a ~3log(10) difference in TCR sensitivity with preserved fine specificity. The high-affinity TCR markedly diminished T cell pathogenicity. T cells were not deleted, did not upregulate Foxp3, and barring disease induction were predominantly naive. However, high-affinity CD4(+) T cells showed an altered cytokine profile characterized by the production of protective cytokines prior to ex

SUBMITTER: Alli R 

PROVIDER: S-EPMC3221875 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature