A conformational change senses the strength of T cell receptor–ligand interaction during thymic selection
- Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, and approved May 5, 2006 (received for review March 3, 2006)
Abstract
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.
Footnotes
- *To whom correspondence should be addressed. E-mail: balarcon{at}cbm.uam.es
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Author contributions: B.A. designed research; R.M.R. and H.M.v.S. performed research; R.M.R., H.M.v.S., and B.A. analyzed data; and B.A. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- DP,
- CD4+CD8+double-positive;
- pMHC,
- peptide antigen-loaded MHC;
- TCR,
- T cell antigen receptor
Abbreviations:
- © 2006 by The National Academy of Sciences of the USA
