Cited by 1,968

The DOI matches its Crossref record.

Three-dimensional segregation of supramolecular activation clusters in T cells

Monks, Colin R. F., Freiberg, Benjamin A., Kupfer, Hannah, Sciaky, Noah, Kupfer, Abraham·1998·Nature

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.

Overview

Integrity signals

Registry

Crossref · 10.1038/25764

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 17

  1. Weiss, A. & Littman, D. R. Signal transduction by lymphocyte antigen receptors. Cell 76, 263–274 (1994). · DOI
  2. Qian, D. & Weiss, A. Tcell antigen receptor signal transduction. Curr. Opin. Cell Biol. 9, 205–212 (1997). · DOI
  3. Monks, C. R., Kupfer, H., Tamir, I., Barlow, A. & Kupfer, A. Selective modulation of protein kinase C-θ during T-cell activation. Nature 385, 83–86 (1997). · DOI
  4. Podack, E. R. & Kupfer, A. T-cell effector functions: mechanisms for delivery of cytotoxicity and help. Annu. Rev. Cell Biol. 7, 479–504 (1991). · DOI
  5. Singer, S. J. Intercellular communication and cell-cell adhesion. Science 255, 1671–1677 (1992). · DOI
  6. Kupfer, A. & Singer, S. J. Cell biology of cytotoxic and helper T cell functions: immunofluorescence microscopic studies of single cells and cell couples. Annu. Rev. Immunol. 7, 309–337 (1989). · DOI
  7. Hiraoka, Y., Sedat, J. W. & Agard, D. A. Determination of three-dimensional imaging properties of a light microscope system. Partial confocal behavior in epifluorescence microscopy. Biophys. J. 57, 325–333 (1990). · DOI
  8. Kupfer, A. & Singer, S. J. The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose. J. Exp. Med. 170, 1697–1713 (1989). · DOI
  9. Kupfer, A., Burn, P. & Singer, S. J. The PMA-induced specific association of LFA-1 and talin in intact cloned T helper cells. J. Mol. Cell. Immunol. 4, 317–325 (1990).
  10. McCloskey, M. A. & Poo, M. M. Contact-induced redistribution of specific membrane components: local accumulation and development of adhesion. J. Cell Biol. 102, 2185–2196 (1986). · DOI
  11. Harding, C. V. & Unanue, E. R. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation. Nature 346, 574–576 (1990). · DOI
  12. Anderson, M. S., Swier, K., Arneson, L. & Miller, J. Enhanced antigen presentation in the absence of the invariant chain endosomal localization signal. J. Exp. Med. 178, 1959–1969 (1993). · DOI
  13. Dittel, B. N., Sant'Angelo, D. B. & Janeway, C. A. J Peptide antagonists inhibit proliferation and the production of IL-4 and/or IFN-gamma in T helper 1, T helper 2, and T helper 0 clones bearing the same TCR. J. Immunol. 158, 4065–4073 (1997). · DOI
  14. Schlessinger, J. SH2/SH3 signaling proteins. Curr. Opin. Genet. Dev. 4, 25–30 (1994). · DOI
  15. Lemmon, M. A., Ferguson, K. M. & Schlessinger, J. PH domains: diverse sequences with a common fold recruit signaling molecules to the cell surface. Cell 85, 621–624 (1996). · DOI
  16. Pawson, T. & Scott, J. D. Signaling through scaffold, anchoring, and adaptor proteins. Science 278, 2075–2080 (1997). · DOI · Paper page
  17. Kupfer, H., Monks, C. R. & Kupfer, A. Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B-antigen presenting cell interactions. J. Exp. Med. 179, 1507–1515 (1994). · DOI

Cited by

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review