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Publication : A conformational change senses the strength of T cell receptor-ligand interaction during thymic selection.

First Author  Risueño RM Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  25 Pages  9625-30
PubMed ID  16766661 Mgi Jnum  J:111034
Mgi Id  MGI:3652644 Doi  10.1073/pnas.0601785103
Citation  Risueno RM, et al. (2006) A conformational change senses the strength of T cell receptor-ligand interaction during thymic selection. Proc Natl Acad Sci U S A 103(25):9625-30
abstractText  T cell antigen receptor (TCR) triggering determines the fate of immature thymocytes. The affinity of the TCR for its endogenous peptide/MHC ligands serves as a signal for positive or negative selection through mechanisms that are still little understood. We have used a conformation-specific antibody to demonstrate that recognition of TCR ligands that lead to negative selection induces a conformational change in the TCR in situ. In contrast, this conformational change is elicited in only a small percentage of immature thymocytes during positive selection. Using a TUNEL assay, we demonstrate that the conformational change in the TCR is strongly linked to activation of programmed cell death in conditions leading to negative selection. Furthermore, the few conformational change-positive thymocytes detected in conditions that preferably lead to positive selection are also TUNEL-positive. Thus, the conformational change in the TCR may underlie the discrimination of ligands leading to positive and negative selection.
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