Mechanisms for T cell receptor triggering

  title={Mechanisms for T cell receptor triggering},
  author={P. Anton van der Merwe and Omer Dushek},
  journal={Nature Reviews Immunology},
There is considerable controversy about the mechanism of T cell receptor (TCR) triggering, the process by which the TCR tranduces signals across the plasma membrane after binding to its ligand (an agonist peptide complexed with an MHC molecule). Three main types of mechanism have been proposed, which involve aggregation, conformational change and segregation. Here, we review recently published evidence for each type of mechanism and conclude that all three may be involved. This complexity may… 

Elementary Steps in T Cell Receptor Triggering

It is proposed that breaking down the process of TCR triggering into tractable elementary steps may be a useful approach in building mechanistic TCR trigger models and once these elementary steps are understood, they can be recombined to build a unified model of T CR triggering.

TCR Signaling: Mechanisms of Initiation and Propagation.

Biophysical Mechanism of T Cell Receptor Triggering in a Reconstituted System

An artificial, chemically controlled receptor system generates the same effect as TCR–pMHC, demonstrating that the binding energy of an extracellular protein–protein interaction can drive the spatial segregation of membrane proteins without a transmembrane conformational change.

Structural understanding of T cell receptor triggering

Structural studies of TCR structure and triggering using diverse biochemical and biophysical tools are synthesized and the relevance of the conformational change model in TCR triggering is discussed.

Initiation of TCR Phosphorylation and Signal Transduction

The initial phase of T cell receptor (TCR) binding to MHC–peptide (MHCp) is quickly followed by a second, stronger, binding phase representing the binding of CD8 to the MHCp, which requires signaling by a Src-family kinase such as Lck.

Molecular mechanisms of T cell sensitivity to antigen

This work reviews experimental and mathematical work that has contributed to uncovering molecular mechanisms of T cell sensitivity, and organizes the mechanisms by where they act in the pathway to activate T cells, namely mechanisms that promote TCR/pMHC binding, induce rapid TCR signaling, and amplify T CR signaling.

Lipid in T-cell receptor transmembrane signaling.

Dual Role of CD4 in Peripheral T Lymphocytes

The current knowledge on CD4 in T cells is summarized, with a special emphasis on the spatio-temporal organization of early signaling events and the relevance for CD4 function, and the capacity of CD4 to interact with the MHC in the absence of TCR is highlighted.



Molecular mechanisms involved in T cell receptor triggering.

Initiation of TCR signalling revisited.

Serial triggering of many T-cell receptors by a few peptide–MHC complexes

It is shown that a small number of peptide–MHC complexes can achieve a high TCR occupancy, because a single complex can serially engage and trigger up to ∼200 TCRs.

T cell receptor engagement by peptide–MHC ligands induces a conformational change in the CD3 complex of thymocytes

It is concluded that TCR engagement with a cognate pMHC ligand induces a conformational change in the CD3 complex of thymocytes and proposed that this marks an initial event during thymic selection that signals the recognition of self-antigen.

The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation.

A model of how self and foreign ligand recognition each evoke the proper responses from T cells, how these two classes of signaling events interact, and how pathologic responses may arise as a result of the underlying properties of the system are synthesized.

Affinity threshold for thymic selection through a T-cell receptor–co-receptor zipper

A new model is proposed that describes how the T CR 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.

Direct observation of ligand recognition by T cells

It is shown that T cells expressing the CD4 antigen respond with transient calcium signalling to even a single agonist peptide–MHC ligand, and that the organization of molecules in the contact zone of the T cell and APC takes on the characteristics of an immunological synapse when only about ten agonists are present.

A role for "self" in T-cell activation.

The molecular basis of TCR germline bias for MHC is surprisingly simple

A reconsideration of the TCR–peptide-MHC structural database shows that not only have the answers been there all along but also they were predictable by the first principles of physical chemistry.

T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand

The results show the importance of the small size of the TCR–pMHC complex and support a role for size-based segregation of cell-surface molecules in TCR triggering.