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J Immunol. 2013 Sep 1;191(5):2064-71. doi: 10.4049/jimmunol.1300523. Epub 2013 Jul 29.

T lymphocytes sense antigens within seconds and make a decision within one minute.

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Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, 13288 Marseille Cedex 09, France.


Adaptive immune responses are triggered by the rapid and sensitive detection of MHC-bound peptides by TCRs. The kinetics of early TCR/APC contacts are incompletely known. In this study, we used total internal reflection fluorescence microscopy to image human T cell membranes near model surfaces: contact was mediated by mobile protrusions of <0.4 μm diameter. The mean lifetime of contacts with a neutral surface was 8.6 s. Adhesive interactions increased mean contact time to 27.6 s. Additional presence of TCR ligands dramatically decreased contact to 13.7 s, thus evidencing TCR-mediated triggering of a pulling motion within seconds after ligand encounter. After an interaction typically involving 30-40 contacts formed during a 1-min observation period, TCR stimulation triggered a rapid and active cell spreading. Pulling events and cell spreading were mimicked by pharmacological phospholipase Cγ1 activation, and they were prevented by phospholipase Cγ1 inhibition. These results provide a quantitative basis for elucidating the earliest cell response to the detection of foreign Ags.

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