Ca2+ Release from the Endoplasmic Reticulum of NY-ESO-1–Specific T Cells Is Modulated by the Affinity of TCR and by the Use of the CD8 Coreceptor

Chen, Ji‐Li; Morgan, Anthony J.; Stewart-Jones, Guillaume; Shepherd, Dawn; Bossi, Giovanna; Wooldridge, Linda; Hutchinson, Sarah; Sewell, Andrew K.; Griffiths, Gillian M.; Merwe, P. Anton van der; Jones, Emma; Galione, Antony; Cerundolo, Vincenzo

doi:10.4049/jimmunol.0902103

Cited by 36 publications

(39 citation statements)

References 68 publications

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“…3b). These results are consistent with previously published data showing that recognition of a strong agonist ligand results in a very rapid onset and fast accumulation of intracellular Ca 2+ , while stimulation with weak agonists significantly delays the onset time and induces much slower accumulation of intracellular Ca 2+ with lower average magnitude1213. Furthermore, the delay of the onset time revealed a poor dependence on the peptide concentration12.…”

Section: Resultssupporting

confidence: 92%

Evaluating frequency and quality of pathogen-specific T cells

et al. 2016

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It is generally accepted that enumeration and characterization of antigen-specific T cells provide essential information about potency of the immune response. Here, we report a new technique to determine the frequency and potency of antigen-specific CD8 T cells. The assay measures changes of intracellular Ca2+ in real time by fluorescent microscopy in individual CD8 T cells responding to cognate peptides. The T cells form continuous monolayer, enabling the cells to present the peptides to each other. This approach allows us to evaluate the kinetics of intracellular Ca2+ signalling that characterizes the quality of T cell response. We demonstrate the usefulness of the assay examining the frequency and quality of cytomegalovirus-specific CD8 T cells from healthy donor and patient after haploidentical stem cell transplantation. The new assay has a potential to provide essential information determining the status of the immune system, disease morbidity, potency of therapeutic intervention and vaccine efficacy.

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Section: Resultssupporting

confidence: 92%

Evaluating frequency and quality of pathogen-specific T cells

et al. 2016

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“…The relationship between TCR-pMHC interaction kinetics and intracellular signaling to cytotoxic granule release was recently clarified in a study that observed efficient centrosome polarization but a decrease in granule recruitment in response to a shorter TCR-pMHC interaction (59). Lower-affinity pMHC ligand also correlates with less cytotoxic granule polarization in tumor-reactive T cells (33). In vivo, studies varying the amount of Ag showed a correlation between pMHC density and CD8 + cytotoxic function (44,60).…”

Section: Tcr-pmhc Interaction Parameters and In Vivo T Cell Immunitymentioning

confidence: 99%

“…Increase in the concentration of intracellular Ca 2+ occurs with a delay after a shorter TCR-pMHC interaction (31) or a lower dose of pMHC ligand (32). A recent study of Ca 2+ dynamics in tumor-reactive T cells showed that a high-affinity pMHC ligand induced sustained Ca 2+ flux and emptying of endoplasmic reticulum Ca 2+ stores, but oscillating Ca 2+ flux and only partial endoplasmic reticulum emptying was observed with a lower-affinity ligand during the time frame examined (33). In addition, recruitment of CD3z to the T cell-APC synapse was delayed in response to a pMHC ligand with a shorter TCR interaction, but normal levels of accumulation (as seen with natural pMHC ligand) were achieved after twice as much time had elapsed (34).…”

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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“…The affinity of a TCR to a given peptide epitope is dependent on its TCR sequence, which impacts the downstream fate (2) and functional capacity (3) of T cells by modulating TCR signaling strength (4) and proliferation rates (3, 5). TCR-pMHC affinity is widely known to be a major determinant in the efficacy of adoptive T cell transfer therapy (ACT).…”

Section: Introductionmentioning

confidence: 99%

Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells

Zhang

Parker

et al. 2016

Sci. Transl. Med.

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T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCR). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. Here, we introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8+ T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications.

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Ca2+ Release from the Endoplasmic Reticulum of NY-ESO-1–Specific T Cells Is Modulated by the Affinity of TCR and by the Use of the CD8 Coreceptor

Abstract: Material

Cited by 36 publications

References 68 publications

Evaluating frequency and quality of pathogen-specific T cells

Evaluating frequency and quality of pathogen-specific T cells

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

Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells

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