A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28

Nat Immunol. 2011 Oct 2;12(11):1105-12. doi: 10.1038/ni.2120.


Protein kinase C-θ (PKC-θ) translocates to the center of the immunological synapse, but the underlying mechanism and its importance in T cell activation are unknown. Here we found that the V3 domain of PKC-θ was necessary and sufficient for localization to the immunological synapse mediated by association with the coreceptor CD28 and dependent on the kinase Lck. We identified a conserved proline-rich motif in V3 required for association with CD28 and immunological synapse localization. We found association with CD28 to be essential for PKC-θ-mediated downstream signaling and the differentiation of T helper type 2 cells (T(H)2 cells) and interleukin 17-producing helper T cells (T(H)17 cells) but not of T helper type 1 cells (T(H)1 cells). Ectopic expression of V3 sequestered PKC-θ from the immunological synapse and interfered with its functions. Our results identify a unique mode of CD28 signaling, establish a molecular basis for the immunological synapse localization of PKC-θ and indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated inflammatory diseases.

Publication types

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

MeSH terms

  • Amino Acid Motifs / genetics
  • Animals
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Immunological Synapses
  • Immunomodulation
  • Isoenzymes / genetics
  • Isoenzymes / immunology
  • Isoenzymes / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Proline-Rich Protein Domains / genetics
  • Protein Binding / immunology
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein Transport / immunology
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*
  • Th2 Cells / pathology


  • CD28 Antigens
  • Isoenzymes
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta