title: T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters.
abstract: T lymphocytes need to detect rare cognate foreign peptides among numerous foreign and self-peptides. This discrimination seems to be based on the kinetics of TCRs binding to their peptide-MHC (pMHC) ligands, but there is little direct information on the minimum time required for processing elementary signaling events and deciding to initiate activation. Here, we used interference reflection microscopy to study the early interaction between transfected human Jurkat T cells expressing the 1G4 TCR and surfaces coated with five different pMHC ligands of 1G4. The pMHC concentration required for inducing 50% maximal IFN-γ production by T cells, and 1G4-pMHC dissociation rates measured in soluble phase or on surface-bound molecules, displayed six- to sevenfold variation among pMHCs. When T cells were dropped onto pMHC-coated surfaces, rapid spreading occurred after a 2-min lag. The initial spreading rate measured during the first 45 s, and the contact area, were strongly dependent on the encountered TCR ligand. However, the lag duration did not significantly depend on encountered ligand. In addition, spreading appeared to be an all-or-none process, and the fraction of spreading cells was tightly correlated to the spreading rate and spreading area. Thus, T cells can discriminate between fairly similar TCR ligands within 2 min.
authors.affiliation: Lab Adhesion Cellulaire and Inflammation, Aix-Marseille Université, France.|INSERM U1067, France.|CNRS, U7333, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Brodovitch
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: Shenderov
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.affiliation: Lab Adhesion Cellulaire and Inflammation, Aix-Marseille Université, France.|INSERM U1067, France.|CNRS, U7333, France.|Assistance Publique, Hôpitaux de Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bongrand
authors.affiliation: Lab Adhesion Cellulaire and Inflammation, Aix-Marseille Université, France.|INSERM U1067, France.|CNRS, U7333, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pierres
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Philip Anton
authors.initials: PA
authors.lastname: van der Merwe
mesh_terms: D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell
keywords: Affinity; Early T-cell activation; Interference reflection microscopy; Kinetics; Spreading; TCR; pMHC