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Three-dimensional segregation of supramolecular activation clusters in T cells
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.
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“Lck and ZAP-70 have been shown to translocate to microclusters of receptors and signaling molecules in the peripheral regions of the T-APC interface within lipid rafts during initiation of the TCR activation signal. The clusters form a central supramolecular activation cluster (c-SMAC) of the IS [24], [25], [26].”
From RhoH Regulates Subcellular Localization of ZAP-70 and Lck in T Cell Receptor Signaling (2010) · cites this paper as [25]
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Metadata
- Authors
- Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N., & Kupfer, A.
- Venue
- Nature
- Published
- 1998-09
- Volume
- 395
- Issue
- 6697
- Pages
- 82-86
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 1,968
- References
- 0
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- 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. https://doi.org/10.1038/25764
