Three-dimensional segregation of supramolecular activation clusters in T cells

Colin R F Monks, Benjamin A. Freiberg, Hannah Kupfer, Noah Sciaky, Abraham Kupfer

Research output: Contribution to journalArticle

Abstract

Activation of T cells by antigen-presenting cells (APCs) depends on the complex integration of signals that are delivered by multiple antigen receptors. Most receptor-proximal activation events in T cells were identified using multivalent anti-receptor antibodies, eliminating the need to use the more complex APCs. As the physiological membrane-associated ligands on the APC and the activating antibodies probably trigger the same biochemical pathways, it is unknown why the antibodies, even at saturating concentrations, fail to trigger some of the physiological T-cell responses. Here we study, at the level of the single cell, the responses of T cells to native ligands. We used a digital imaging system and analysed the three- dimensional distribution of receptors and intracellular proteins that cluster at the contacts between T cells and APCs during antigen-specific interactions. Surprisingly, instead of showing uniform oligomerization, these proteins clustered into segregated three-dimensional domains within the cell contacts. The antigen-specific formation of these new, spatially segregated supramolecular activation clusters may generate appropriate physiological responses and may explain the high sensitivity of the T cells to antigen.

Original languageEnglish (US)
Pages (from-to)82-86
Number of pages5
JournalNature
Volume395
Issue number6697
DOIs
StatePublished - Sep 3 1998
Externally publishedYes

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Antigen-Presenting Cells
T-Lymphocytes
Antigens
Ligands
Antigen Receptors
Antibodies
Viral Tumor Antigens
Anti-Idiotypic Antibodies
Proteins
Membranes

ASJC Scopus subject areas

  • General

Cite this

Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N., & Kupfer, A. (1998). Three-dimensional segregation of supramolecular activation clusters in T cells. Nature, 395(6697), 82-86. https://doi.org/10.1038/25764

Three-dimensional segregation of supramolecular activation clusters in T cells. / Monks, Colin R F; Freiberg, Benjamin A.; Kupfer, Hannah; Sciaky, Noah; Kupfer, Abraham.

In: Nature, Vol. 395, No. 6697, 03.09.1998, p. 82-86.

Research output: Contribution to journalArticle

Monks, CRF, Freiberg, BA, Kupfer, H, Sciaky, N & Kupfer, A 1998, 'Three-dimensional segregation of supramolecular activation clusters in T cells', Nature, vol. 395, no. 6697, pp. 82-86. https://doi.org/10.1038/25764
Monks CRF, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998 Sep 3;395(6697):82-86. https://doi.org/10.1038/25764
Monks, Colin R F ; Freiberg, Benjamin A. ; Kupfer, Hannah ; Sciaky, Noah ; Kupfer, Abraham. / Three-dimensional segregation of supramolecular activation clusters in T cells. In: Nature. 1998 ; Vol. 395, No. 6697. pp. 82-86.
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