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T cell antigen recognition requires T cell antigen receptors (TCRs) engaging MHC-embedded antigenic peptides (pMHCs) within the contact region of a T cell with its conjugated antigen-presenting cell. Despite micromolar TCR:pMHC affinities, T cells respond to even a single antigenic pMHC, and higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. We interrogated the stoichiometry of TCRs and their associated CD3 subunits on the surface of living T cells through single-molecule brightness and single-molecule coincidence analysis, photon-antibunching-based fluorescence correlation spectroscopy and Förster resonance energy transfer measurements. We found exclusively monomeric TCR-CD3 complexes driving the recognition of antigenic pMHCs, which underscores the exceptional capacity of single TCR-CD3 complexes to elicit robust intracellular signaling.

Original publication

DOI

10.1038/s41590-018-0092-4

Type

Journal article

Journal

Nat Immunol

Publication Date

05/2018

Volume

19

Pages

487 - 496

Keywords

Animals, Antigen Presentation, CD3 Complex, Lymphocyte Activation, Mice, Mice, Transgenic, Receptors, Antigen, T-Cell, T-Lymphocytes