title: Protein kinase C delta is a critical regulator of CD1d-mediated antigen presentation.
abstract: We have recently demonstrated that the p38 and ERK1/2 MAP kinases play reciprocal roles in the control of CD1d-mediated antigen presentation. Although the use of specific inhibitors for these pathways clearly had an effect, the effects were not complete, leading to speculations that additional pathways were involved. Here, we show that inhibiting protein kinase C delta (PKCdelta) substantially impairs antigen presentation by murine CD1d1 to NKT cells. This effect was accompanied by marked changes in the intracellular localization of CD1d. Expression of a dominant-negative mutant of PKCdelta in CD1d(+) cells resulted in nearly undetectable endogenous antigen presentation, substantially impaired CD1d recycling, a decrease in MAPK activation, and a decrease in the ability to present low (but not high) concentrations of alpha-galactosylceramide at the cell surface. These data strongly suggest that PKCdelta is a critical regulator of CD1d-mediated antigen presentation and is involved in multiple steps of the process.
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. rbrutkie@iupui.edu
authors: Randy R
authors: RR
authors: Brutkiewicz
authors: Claire A
authors: CA
authors: Willard
authors: Kristin K
authors: KK
authors: Gillett-Heacock
authors: M Robert
authors: MR
authors: Pawlak
authors: Jennifer C
authors: JC
authors: Bailey
authors: Masood A
authors: MA
authors: Khan
authors: Manjula
authors: M
authors: Nagala
authors: Wenjun
authors: W
authors: Du
authors: Jacquelyn
authors: J
authors: Gervay-Hague
authors: Gourapura J
authors: GJ
authors: Renukaradhya
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism*; D055610:Antigens, CD1d; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D051379:Mice; D009154:Mutation / Q000235:genetics; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D018949:Antigens, CD1; D055610:Antigens, CD1d; D001578:Benzopyrans; D047428:Protein Kinase Inhibitors; C085746:rottlerin; D051745:Protein Kinase C-delta