title: T lymphocytes sense antigens within seconds and make a decision within one minute.
abstract: 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.
authors.affiliation: Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, 13288 Marseille Cedex 09, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Brodovitch
authors.forename: Pierre
authors.initials: P
authors.lastname: Bongrand
authors.forename: Anne
authors.initials: A
authors.lastname: Pierres
mesh_terms: D000941:Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008856:Microscopy, Fluorescence / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013995:Time
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell