TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells

Fan Xia, Cheng-Rui Qian, Zhou Xun, Yannick Hamon (), Anne-Marie Sartre, Anthony Formisano, Sébastien Mailfert (), Marie-Claire Phelipot, Cyrille Billaudeau (), Sébastien Jaeger, Jacques Nunès (), Xiao-Jun Guo and Hai-Tao He
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Fan Xia: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Cheng-Rui Qian: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Zhou Xun: AMSE - Aix-Marseille Sciences Economiques - EHESS - École des hautes études en sciences sociales - AMU - Aix Marseille Université - ECM - École Centrale de Marseille - CNRS - Centre National de la Recherche Scientifique
Yannick Hamon: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Anne-Marie Sartre: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Anthony Formisano: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Sébastien Mailfert: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Marie-Claire Phelipot: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Cyrille Billaudeau: LPN - Laboratoire de photonique et de nanostructures - CNRS - Centre National de la Recherche Scientifique
Sébastien Jaeger: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Jacques Nunès: CRCM - Centre de Recherche en Cancérologie de Marseille - AMU - Aix Marseille Université - IPC - Institut Paoli-Calmettes - Fédération nationale des Centres de lutte contre le Cancer (FNCLCC) - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Xiao-Jun Guo: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique
Hai-Tao He: CIML - Centre d'Immunologie de Marseille - Luminy - AMU - Aix Marseille Université - INSERM - Institut National de la Santé et de la Recherche Médicale - CNRS - Centre National de la Recherche Scientifique

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Abstract: T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent stimulation of both the TCR and costimulatory receptors remains poorly understood. Here, we explore this issue by analyzing calcium response as a key early signaling event to elicit T cell activation. Experiments using mouse naive CD4+ T cells showed that engagement of the TCR or CD28 with the respective cognate ligand was able to trigger a rise in fluctuating calcium mobilization levels, as shown by the frequency and average response magnitude of the reacting cells compared with basal levels occurred in unstimulated cells. The engagement of both TCR and CD28 enabled a further increase of these two metrics. However, such increases did not sufficiently explain the importance of the CD28 pathways to the functionally relevant calcium responses in T cell activation. Through the autocorrelation analysis of calcium time series data, we found that combined but not separate TCR and CD28 stimulation significantly prolonged the average decay time (τ) of the calcium signal amplitudes determined with the autocorrelation function, compared with its value in unstimulated cells. This increasement of decay time (τ) uniquely characterizes the fluctuating calcium response triggered by concurrent stimulation of TCR and CD28, as it could not be achieved with either stronger TCR stimuli or by coengaging both TCR and LFA-1, and likely represents an important feature of competent early signaling to provoke efficient T cell activation. Our work has thus provided new insights into the interplay between the TCR and CD28 early signaling pathways critical to trigger naive T cell activation.

Keywords: T cell activation; naive T cells; co-stimulation; CD28; TCR-T cell receptor; calcium signaling (search for similar items in EconPapers)
Date: 2018-12
Note: View the original document on HAL open archive server: https://amu.hal.science/hal-02084941v1
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Published in Frontiers in Immunology, 2018, 9, ⟨10.3389/fimmu.2018.02864⟩

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Persistent link: https://EconPapers.repec.org/RePEc:hal:journl:hal-02084941

DOI: 10.3389/fimmu.2018.02864

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