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M. Brameshuber, F. Kellner, B. Rossboth, H. Ta, K. Alge, E. Sevcsik, J. Göhring, M. Axmann, F. Baumgart, N. Gascoigne, S. Darvis, H. Stockinger, G. Schütz, J. Huppa:
"Monomeric TCRs Drive T-Cell Antigen Recognition";
Nature Immunology, 5 (2018), 487 - 496.

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.