4.8 Article

Durable Interactions of T Cells with T Cell Receptor Stimuli in the Absence of a Stable Immunological Synapse

Journal

CELL REPORTS
Volume 22, Issue 2, Pages 340-349

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2017.12.052

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Funding

  1. NIH [PN2 EY016586, R37 AI43542]
  2. Cancer Research Institute post-doctoral fellowship
  3. Wellcome Trust Principal Research Fellowship from Kennedy Trust for Rheumatology Research grant [100262/Z/12/Z, MSP121321]
  4. Human Frontiers Science Program research grant [RGP0033/2015]
  5. European Research Council grant [AdG 670930-SYNECT]

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T cells engage in two modes of interaction with antigen-presenting surfaces: stable synapses and motile kinapses. Although it is surmised that durable interactions of T cells with antigen-presenting cells involve synapses, in situ 3D imaging cannot resolve the mode of interaction. We have established in vitro 2D platforms and quantitative metrics to determine cell-intrinsic modes of interaction when T cells are faced with spatially continuous or restricted stimulation. All major resting human T cell subsets, except memory CD8 T cells, spend more time in the kinapse mode on continuous stimulatory surfaces. Surprisingly, we did not observe any concordant relationship between the mode and durability of interaction on cell-sized stimulatory spots. Naive CD8 T cells maintain kinapses for more than 3 hr before leaving stimulatory spots, whereas their memory counterparts maintain synapses for only an hour before leaving. Thus, durable interactions do not require stable synapses.

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