TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways - PubMed (original) (raw)
doi: 10.1038/ni895. Epub 2003 Feb 10.
Affiliations
- PMID: 12577055
- DOI: 10.1038/ni895
TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
Irena Stefanová et al. Nat Immunol. 2003 Mar.
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.
Comment in
- Tuning the immune system: competing positive and negative feedback loops.
Mueller DL. Mueller DL. Nat Immunol. 2003 Mar;4(3):210-1. doi: 10.1038/ni0303-210. Nat Immunol. 2003. PMID: 12605227 No abstract available.
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