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ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse

E J Allenspach1, P Cullinan, J Tong

  • 1Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Immunity
|December 1, 2001
PubMed

Insights

The large mucin CD43 moves away from T cell interaction sites, organized by ERM proteins. This movement is crucial for T cell activation, impacting cytokine production like IL-2 and IFN-gamma.

Area of Science:

  • Immunology
  • Cell Biology
  • Cytoskeletal Dynamics

Background:

  • CD43 (leukosialin) is a large mucin expressed on T cells.
  • Immune cell interactions involve dynamic protein organization at the cell surface.
  • The role of CD43 localization in T cell activation is not fully understood.

Purpose of the Study:

  • To investigate the mechanism of CD43 exclusion from the T cell/APC immunological synapse.
  • To determine the role of ERM proteins in CD43 localization and T cell activation.

Main Methods:

  • Immunofluorescence microscopy to track CD43 and ERM protein localization.
  • Expression of dominant-negative ERM mutants in T cells.
  • Measurement of cytokine production (IL-2, IFN-gamma) and cell surface marker upregulation (CD69).

Main Results:

  • CD43 actively accumulates in a membrane domain distal to the T cell receptor engagement site.
  • The cytoplasmic tail of CD43 is essential for this distal localization.
  • ERM proteins colocalize with CD43 and are required for its distal accumulation.
  • Inhibition of ERM function impairs IL-2 and IFN-gamma production but not CD69 upregulation or PKC(theta) focusing.

Conclusions:

  • ERM proteins organize a protein complex distal to the immunological synapse.
  • The exclusion of CD43 from the synapse, mediated by ERM proteins, is important for full T cell activation.
  • This suggests that removing inhibitory proteins from the immunological synapse is a key aspect of T cell activation.

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