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Nat Immunol. 2016 Apr;17(4):379-86. doi: 10.1038/ni.3386. Epub 2016 Feb 22.

Control of T cell antigen reactivity via programmed TCR downregulation.

Author information

1
Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
2
Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Abstract

The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity. Thus, programmed downregulation of TCR expression represents a negative feedback mechanism for constraining T cell effector function with a suitable time delay to thereby allow pathogen control while avoiding excess inflammatory damage.

PMID:
26901151
PMCID:
PMC4803589
DOI:
10.1038/ni.3386
[Indexed for MEDLINE]
Free PMC Article

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