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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. Keywords: Affinity r Early T-cell activation r Interference reflection microscopy r Kinetics r pMHC r Spreading r TCR Additional supporting information may be found in the online version of this article at the publisher's web-site
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Alexandre Brodovitch, Eugene Shenderov, Vincenzo Cerundolo, Pierre Bongrand, Anne Pierres, et al.. T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters. European Journal of Immunology, Wiley-VCH Verlag, 2015, 45 (6), pp.1635 - 1642. ⟨10.1002/eji.201445214⟩. ⟨hal-01787585⟩

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