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Publication : Control of T cell antigen reactivity via programmed TCR downregulation.

First Author  Gallegos AM Year  2016
Journal  Nat Immunol Volume  17
Issue  4 Pages  379-86
PubMed ID  26901151 Mgi Jnum  J:258698
Mgi Id  MGI:6140451 Doi  10.1038/ni.3386
Citation  Gallegos AM, et al. (2016) Control of T cell antigen reactivity via programmed TCR downregulation. Nat Immunol 17(4):379-86
abstractText  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.
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