Journal
NATURE REVIEWS IMMUNOLOGY
Volume 9, Issue 3, Pages 206-212Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nri2469
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Funding
- Swiss National Science Foundation, Sybilla (EU FP7)
- National Institutes of Health, Roche
- Novartis
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The affinity of the T-cell receptor (TCR) for self antigen is the basis for the selection of a useful (MHC-restricted) and safe (self-tolerant) T-cell repertoire. However, it has been difficult to understand how thymocytes measure ligand affinity and translate this signal into a cellular response. In this Opinion article, we propose a new model that describes how the TCR discriminates between low- and high-affinity ligands, which is based on the duration of TCR-ligand interactions and a 'zipper' mechanism that mediates the interaction of the TCR and co-receptor molecules to initiate negative-selection signalling.
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