Organization of the resting TCR in nanoscale oligomers

Authors

  • Wolfgang W. A. Schamel,

    1. Department of Molecular Immunology, Institute of Biology III, Faculty of Biology, BIOSS Centre for Biological Signaling Studies, University of Freiburg; and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg, Freiburg, Germany
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  • Balbino Alarcón

    Corresponding author
    1. Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Madrid, Spain
    • Department of Molecular Immunology, Institute of Biology III, Faculty of Biology, BIOSS Centre for Biological Signaling Studies, University of Freiburg; and Centre for Chronic Immunodeficiency CCI, University Clinics Freiburg, Freiburg, Germany
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Correspondence to:

Balbino Alarcón

Centro de Biología Molecular Severo Ochoa

CSIC-Universidad Autónoma de Madrid

Cantoblanco, Madrid 28049, Spain

Tel.: + 34 911964555

Fax: + 34 911964420

E-mail: balarcon@cbm.uam.es

Abstract

Summary

Despite the low affinity of the T-cell antigen receptor (TCR) for its peptide/major histocompatibility complex (pMHC) ligand, T cells are very sensitive to their antigens. This paradox can be resolved if we consider that the TCR may be organized into pre-existing oligomers or nanoclusters. Such structures could improve antigen recognition by increasing the functional affinity (avidity) of the TCR–pMHC interaction and by allowing cooperativity between individual TCRs. Up to approximately 20 TCRs become tightly apposed in these nanoclusters, often in a linear manner, and such structures could reflect a relatively generalized phenomenon: the non-random concentration of membrane receptors in specific areas of the plasma membrane known as protein islands. The association of TCRs into nanoclusters can explain the enhanced kinetics of the pMHC–TCR interaction in two dimensional versus three dimensional systems, but also their existence calls for a revision of the TCR triggering models based on pMHC-induced TCR clustering. Interestingly, the B-cell receptor and the FcεRI have also been shown to form nanoclusters, suggesting that the formation of pre-existing receptor oligomers could be widely used in the immune system.

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