TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
Top Cited Papers
- 10 February 2003
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 4 (3) , 248-254
- https://doi.org/10.1038/ni895
Abstract
Functional discrimination between structurally similar self and foreign antigens is a main attribute of adaptive immunity. Here we describe two feedback mechanisms in T lymphocytes that together sharpen and amplify initial signaling differences related to the quality of T cell receptor (TCR) engagement. Weakly binding ligands predominantly trigger a negative feedback loop leading to rapid recruitment of the tyrosine phosphatase SHP-1, followed by receptor desensitization through inactivation of Lck kinase. In contrast, strongly binding ligands efficiently activate a positive feedback circuit involving Lck modification by ERK, preventing SHP-1 recruitment and allowing the long-lasting signaling necessary for gene activation. The characteristics of these pathways suggest that they constitute an important part of the mechanism allowing T cells to discriminate between self and foreign ligands.Keywords
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