Visualizing TCR-induced POLKADOTS formation and NF-κB activation in the D10 T-cell clone and mouse primary effector T cells

Methods Mol Biol. 2015:1280:219-38. doi: 10.1007/978-1-4939-2422-6_12.

Abstract

T cells are an immune cell lineage that play a central role in protection against pathogen infection. Antigen, in the form of pathogen-derived peptides, stimulates the T-cell receptor (TCR), leading to activation of the transcription factor, nuclear factor kappa B (NF-κB). The subsequent NF-κB-dependent gene expression program drives expansion and effector differentiation of antigen-specific T cells, leading to the adaptive anti-pathogen immune response. The cell surface TCR transmits activating signals to cytosolic NF-κB by a complex signaling cascade, in which the adapter protein Bcl10 plays a key role. We have previously demonstrated that TCR engagement leads to the formation of cytosolic Bcl10 clusters, called POLKADOTS, that provide a platform for the assembly of the terminal signaling complex that ultimately mediates NF-κB activation. In this chapter, we describe the methods utilized to visualize the formation of TCR-induced POLKADOTS and to study the temporal association between POLKADOTS formation and nuclear translocation of the NF-κB subunit, RelA/p65.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens / immunology
  • B-Cell CLL-Lymphoma 10 Protein
  • Cell Differentiation
  • Cloning, Molecular
  • Enzyme Activation
  • Genes, Reporter
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • NF-kappa B / metabolism*
  • Receptors, Antigen, T-Cell / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae / genetics
  • Signal Transduction*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins