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

doi:10.1038/s41590-018-0092-4

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

Research Center Linz

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91 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	487-496
Number of pages	10
Journal	Nature Immunology
Volume	19
Issue number	5
DOIs	https://doi.org/10.1038/s41590-018-0092-4
Publication status	Published - Apr 2018

Keywords

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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10.1038/s41590-018-0092-4

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title = "Monomeric TCRs drive T cell antigen recognition.",

abstract = "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 F{\"o}rster 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.",

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year = "2018",

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doi = "10.1038/s41590-018-0092-4",

language = "English",

volume = "19",

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T1 - Monomeric TCRs drive T cell antigen recognition.

AU - Brameshuber, M

AU - Kellner, F

AU - Rossboth, BK

AU - Ta, H

AU - Alge, K

AU - Sevcsik, E

AU - Göhring, J

AU - Axmann, M

AU - Baumgart, F

AU - Gascoigne, NRJ

AU - Davis, SJ

AU - Stockinger, H

AU - Schütz, GJ

AU - Huppa, JB

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

KW - Animals

KW - Antigen Presentation/immunology

KW - CD3 Complex/chemistry

KW - Lymphocyte Activation/immunology

KW - Mice

KW - Mice, Transgenic

KW - Receptors, Antigen, T-Cell/chemistry

KW - T-Lymphocytes/immunology

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U2 - 10.1038/s41590-018-0092-4

DO - 10.1038/s41590-018-0092-4

M3 - Article

C2 - 29662172

SN - 1529-2908

VL - 19

SP - 487

EP - 496

JO - Nature Immunology

JF - Nature Immunology

IS - 5

ER -

Monomeric TCRs drive T cell antigen recognition.

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Keywords

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