Monomeric TCRs drive T cell antigen recognition.

M Brameshuber, F Kellner, BK Rossboth, H Ta, K Alge, E Sevcsik, J Göhring, M Axmann, F Baumgart, NRJ Gascoigne, SJ Davis, H Stockinger, GJ Schütz, JB Huppa

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89 Citations (Scopus)


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 languageEnglish
Pages (from-to)487-496
Number of pages10
JournalNature Immunology
Issue number5
Publication statusPublished - Apr 2018


  • Animals
  • Antigen Presentation/immunology
  • CD3 Complex/chemistry
  • Lymphocyte Activation/immunology
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell/chemistry
  • T-Lymphocytes/immunology


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