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Protein kinase C delta is a critical regulator of CD1d-mediated antigen presentation

Randy R Brutkiewicz1, Claire A Willard, Kristin K Gillett-Heacock

  • 1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. rbrutkie@iupui.edu

European Journal of Immunology
|August 21, 2007
PubMed

Insights

Protein kinase C delta (PKCdelta) significantly hinders CD1d-mediated antigen presentation to NKT cells. This suggests PKCdelta is a key regulator in CD1d antigen presentation, affecting intracellular localization and recycling.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • p38 and ERK1/2 MAP kinases have known roles in CD1d antigen presentation.
  • Previous studies using inhibitors showed incomplete effects, suggesting other pathways are involved.

Purpose of the Study:

  • To investigate the role of protein kinase C delta (PKCdelta) in CD1d-mediated antigen presentation.
  • To determine if PKCdelta influences CD1d trafficking and NKT cell activation.

Main Methods:

  • Inhibition of PKCdelta in murine CD1d1 cells.
  • Expression of dominant-negative PKCdelta mutant.
  • Analysis of CD1d intracellular localization and recycling.
  • Assessment of antigen presentation to NKT cells.
  • Measurement of MAPK activation.

Main Results:

  • PKCdelta inhibition substantially impaired antigen presentation by CD1d1 to NKT cells.
  • CD1d intracellular localization and recycling were significantly altered.
  • Dominant-negative PKCdelta expression reduced MAPK activation and antigen presentation, particularly at low antigen concentrations.
  • PKCdelta appears to regulate multiple steps in CD1d-mediated antigen presentation.

Conclusions:

  • PKCdelta is a critical regulator of CD1d-mediated antigen presentation.
  • PKCdelta influences CD1d trafficking, MAPK activation, and the presentation of specific antigens to NKT cells.

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