Current Biology
Research PaperAntigen recognition by helper T cells elicits a sequence of distinct changes of their shape and intracellular calcium
Section snippets
Background:
The physiological signal necessary for helper T-cell activation is delivered by a prolonged interaction between the T cell and an antigen-presenting cell (reviewed in [1]). The antigen-specific signal begins with the recognition by the T-cell receptor of an antigen fragment associated with a MHC class II molecule. This triggers a cascade of transduction events, initiated by the CD3 molecule associated with the T-cell receptor (see [2] for review). Other interactions between the T cell and
First phase of the antigen-presenting cell–T cell interaction
When T cells were allowed to settle on a monolayer of L cells in the absence of antigen, most of the T cells were roughly spherical and remained so throughout the duration of the experiment. Under these conditions, adhesion of T cells to L cells was never stable, as the T cells could move when the dish was tipped slightly. Some T cells presented deformations, but these did not appear related to interaction with L cells. The magnitude of these deformations and the percentage of deformed T cells
Discussion
In this paper, we have studied the interaction between helper T lymphocytes and antigen-presenting cells in a simplified biological system (murine artificial antigen-presenting cells, human T cells). The advantage of this system is that cell–cell interactions in the absence of antigen were too weak to allow stable adhesion between the two cell types, and therefore could be considered negligible. The first events observed when the antigen was presented were therefore necessarily a direct
Cells
T-cell clone P28D (P28 cells), specific for diphtheria toxoid (DT) was derived from a HLA-DR6/7 healthy individual as previously described [37]. The clone was propagated in complete culture medium (RPMI 1640 supplemented with 5 % pooled human AB serum, 2 mM L-glutamine, 1 mM Na pyruvate, 50 U ml–1 penicillin, and 50 μgm l–1 streptomycin) by periodic restimulation with the antigen presented by an autologous Epstein-Barr virus transformed B-cell line. Medium containing interleukin-2 (IL-2, final
Acknowledgements
This work was supported by grants from Centre National de la Recherche Scientifique, including an ATIPE grant, and Université Pierre et Marie Curie. E.D. was supported by a grant from the Association de Recherche contre le Cancer. We thank Y.P. Tan for the filter exchange system, C. Randriamampita, M.A. Deugnier and P. Deterre for their comments on the manuscript.
E. Donnadieu, A. Trautmann (corresponding author), Laboratoire de Neurobiologie, CNRS URA 1857, Ecole Normale Supérieure, 46, rue d’Ulm, 75005 Paris, France.
G.Bismuth, Laboratoire d’Immunologie Cellulaire et Tissulaire, CNRS URA 625, CERVI, Centre Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
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2019, Seminars in Cell and Developmental BiologyCitation Excerpt :The authors also concluded that Ca2+ signals were global and not different at or away from the IS and that the large Ca2+ entry during phase II was intimately connected to the loss of T cell motility, which was still present in phase I. Phase III of the antigen recognition was characterized by new deformations of the T cells and accompanied by a global more steady [Ca2+]int rise. In contrast to the first two phases, phase III could not be mimicked by any non-focal “artificial” T cell stimulation, for instance with thapsigargin [87]. Finally Donnadieu et al. report that low-level TCR stimulation can elicit T cell proliferation at very low [Ca2+]int < 400 nM and that Ca2+ oscillations show no advantage against a simple sustained [Ca2+]int rise [88].
Obstacles to T cell migration in the tumor microenvironment
2019, Comparative Immunology, Microbiology and Infectious DiseasesCitation Excerpt :Experiments performed in vitro and corroborated in vivo provided the evidence that presentation of the cognate antigen leads to a stable T cell - APC interaction that functions as a “tether” restricting entrapped T cells from migrating [19]. Several factors are instrumental in provoking this arrest, including an increase in intracellular Ca2+ and the activation of adhesion molecules, mainly integrins [20]. Moreover, this cell-cell interaction is strongly dependent on the strength of the signal received by the T lymphocyte.
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2017, Advanced Drug Delivery ReviewsCitation Excerpt :During the formation of a mature immunological synapse, the T-Cell will also undergo morphological change by flattening its surface to allow for maximal cellular contact. Within 2–15 min of a T-Cell contacting a cognate dendritic cell, it has been observed that T-Cells will flatten out over the surface of the APC (Fig. 5) [100,101]. This morphological change observed in T-Cells has been attributed to intracellular calcium signaling which subsequently controls several aspects of T-Cell polarization and migration [102].
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E. Donnadieu, A. Trautmann (corresponding author), Laboratoire de Neurobiologie, CNRS URA 1857, Ecole Normale Supérieure, 46, rue d’Ulm, 75005 Paris, France.
G.Bismuth, Laboratoire d’Immunologie Cellulaire et Tissulaire, CNRS URA 625, CERVI, Centre Hospitalier Pitié-Salpêtrière, 75013 Paris, France.