T cells like a firm molecular handshake

Dustin, Michael L.; Zhu, Cheng

doi:10.1073/pnas.0600899103

Cited by 16 publications

(16 citation statements)

References 19 publications

(21 reference statements)

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“…As described in Materials and Methods, titrations of the tetramers at equilibrium were done as part of apparent K D analysis (Figure S2B,C) [27], which shows that K5/I-E k tetramers bind to 5C.C7 T cells with relatively higher avidity than MCC/I-E k tetramers. The larger difference in the equilibrium K5 and MCC measurements seen with tetrameric pMHC and T cells (Figure S2) versus solution measurements with monomeric pMHC and TCR (Figure 1, Table 1) could be explained by a greater effective affinity due to the two-dimensional confinement imposed by the T cell membrane [28]–[30]. k d is likely to be the more important determinant of pMHC ligand potency in this case [10], especially given the small association rates of the 5C.C7 TCR/pMHC complexes (k a ∼10 3 M −1 s −1 ; Table 1) [13].…”

Section: Resultsmentioning

confidence: 99%

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

et al. 2010

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Section: Resultsmentioning

confidence: 99%

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

et al. 2010

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“…Several theories on T‐cell triggering have been proposed to explain how recognition of pMHC by a weakly interacting (approximately 1–100 μM K d ) clonotypic αβ heterodimer on the T‐cell surface evokes intracellular signaling via the adjacent CD3 components with minimal, if any, stable αβ ectodomain interface contacts . These include conformational change, aggregation, and segregation models.…”

Section: The αβ Tcr Complex and Mechanotransductionmentioning

confidence: 99%

The structural basis of αβ T‐lineage immune recognition: TCR docking topologies, mechanotransduction, and co‐receptor function

Wang

Reinherz

2012

Immunological Reviews

102

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Summary Self versus non-self discrimination is at the core of T lymphocyte recognition. To this end, αβ T-cell receptors (TCRs) ligate ‘foreign’ peptides bound to major histocompatibility complex (MHC) class I or class II molecules (pMHC) arrayed on the surface of antigen-presenting cells (APCs). Since the discovery of TCRs ~30 years ago, considerable structural and functional data have detailed the molecular basis of their extraordinary ligand specificity and sensitivity in mediating adaptive T-cell immunity. This review focuses on the structural biology of the Fab-like TCRαβ clonotypic heterodimer and its unique features in conjunction with those of the associated CD3εγ and CD3εδ heterodimeric molecules, which, along with CD3ζζ homodimer, comprise the TCR complex in a stoichiometry of 1:1:1:1. The basis of optimized TCRαβ docking geometry on the pMHC linked to TCR mechanotransduction and required for T-cell signaling as well as CD4 and CD8 co-receptor function are detailed. A model of the TCR ectodomain complex including its connecting peptides suggests how force generated during T-cell immune surveillance and at the immunological synapse results in dynamic TCR quaternary change involving its heterodimeric components. Potential insights from the structural biology relevant to immunity and immunosuppression are revealed.

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“…Thus, consideration of TCR-pMHC binding according to any single parameter such as off-rate or affinity is likely to be limited in applicability. In addition, physical constraints imposed by the juxtaposition of the T cell and APC membranes almost certainly influence TCR binding to pMHC (26)(27)(28).…”

Section: Tcr-pmhc Binding Parameters: Definitions and Controversiesmentioning

confidence: 99%

Strength of TCR–Peptide/MHC Interactions and In Vivo T Cell Responses

Corse

Gottschalk

Allison

2011

The Journal of Immunology

176

163

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The TCR can detect subtle differences in the strength of interaction with peptide/MHC ligand and transmit this information to influence downstream events in T cell responses. Manipulation of the factor commonly referred to as TCR signal strength can be achieved by changing the amount or quality of peptide/MHC ligand. Recent work has enhanced our understanding of the many variables that contribute to the apparent cumulative strength of TCR stimulation during immunogenic and tolerogenic T cell responses. In this review, we consider data from in vitro studies in the context of in vivo immune responses and discuss in vivo consequences of manipulation of strength of TCR stimulation, including influences on T cell–APC interactions, the magnitude and quality of the T cell response, and the types of fate decisions made by peripheral T cells.

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T cells like a firm molecular handshake

Cited by 16 publications

References 19 publications

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

The structural basis of αβ T‐lineage immune recognition: TCR docking topologies, mechanotransduction, and co‐receptor function

Strength of TCR–Peptide/MHC Interactions and In Vivo T Cell Responses

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