Pulling on the TCR

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Science  14 Mar 2008:
Vol. 319, Issue 5869, pp. 1461
DOI: 10.1126/science.319.5869.1461c

The exact mechanism by which peptide-loaded major histocompatibility complex (pMHC) activates the T cell receptor (TCR) has been controversial. Effective TCR activation requires presentation by antigen-presenting cellssoluble pMHC cannot activate T cells. In the presence of endogenous pMHC, however, very low concentrations of agonist pMHC are required to activate TCR signaling, as are costimulatory interactions. Ma et al. anchored pMHCs to lipid bilayers or plastic surfaces and found that in the absence of nonagonist pMHC, a minimum of 1 to 10 monomeric agonist pMHCs (MCC-loaded pMHC) per T cell was sufficient to stimulate TCR signaling in T cells interacting with the artificial substrates. Furthermore, the T cell response (calcium signal) was not enhanced by the addition of nonagonist pMHC with the agonist pMHC or under conditions where the nonagonist pMHC and agonist pMHC were close enough to function as a dimer. When murine B cell lymphoma cells were loaded with various endogenous peptides and the MCC peptide, the production of interleukin-2 by the T cells was the same whether a costimulatory endogenous pMHC was present or not. In further experiments, adhesion was shown to be necessary for TCR triggering, as was the actin cytoskeleton. The authors propose a model whereby the agonist pMHC-TCR interaction leads to receptor deformation and activation when the cytoskeleton provides a pulling force on the complex. Endogenous pMHC-TCR interactions would be insufficiently strong to provide the necessary activation signal, and the complex would dissociate when pulled on by the cytoskeleton. NRG

PLoS Biol. 6, e43 (2008).

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