Wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocks the assembly of peptide-MHC class II complexes

International Immunology
W SongS K Pierce

Abstract

Peptide-class II complexes are assembled in endocytic, lysosome-like compartments where newly synthesized class II molecules are targeted from the trans-Golgi network (TGN). Recent studies have implicated phosphatidylinositol 3-kinase (PI3-kinase) as an essential component in membrane trafficking from the TGN to lysosomes. Here, using subcellular fractionation, we show PI3-kinase activity associated with subcellular fractions which contain the class II peptide-loading compartment (IIPLC) in B cells. At concentrations required for inhibition of PI3-kinase activity in vivo, wortmannin blocked the processing and presentation of antigen by B cells to T cells. Treatment of B cells with wortmannin significantly limited the proteolytic degradation of invariant chain and the formation of peptide-class II complexes. Subcellular fractionation coupled with pulse-chase analyses showed that invariant chain and class II molecules trafficked to the IIPLC in wortmannin-treated cells. However, wortmannin prevented the maturation and correct targeting to the IIPLC of cathepsin D, a protease necessary for the degradation of invariant chain and assembly of processed antigen-class II complexes. These results suggest that li-class II complexes traff...Continue Reading

Citations

Nov 30, 2006·Current Opinion in Immunology·Andrew B Strawbridge, Janice S Blum
Mar 31, 2005·Advances in Cancer Research·Marije MarsmanJacques Neefjes
Dec 3, 2002·The Journal of Biological Chemistry·Marie GranboulanClaire Hivroz
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monther M Al-AlwanAaron J Marshall
Jan 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine LauChung-Wai Chow
Aug 7, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·James B ChungJohn G Monroe
Jun 16, 2004·Immunological Investigations·Erica M McGovernJames R Drake
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keshab Chandra RoyVipin Kumar

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