Phosphorylation of the invariant chain by protein kinase C regulates MHC class II trafficking to antigen-processing compartments

The invariant chain (Ii) plays a critical role in the transport of newly sy nthesized class II molecules to endosomal Ag-processing compartments. Of th e two major isoforms of human Ii, only Ii-p35 is phosphorylated in vivo, an d inhibiting Ii phosphorylation inhibits the trafficking of newly synthesiz ed class II molecules to Ag-processing compartments. We now report that a m ember of the protein kinase C family of serine/threonine kinases is respons ible for the constitutive phosphorylation of 50% of the total cellular pool of Ii-p35 in a wide variety of APCs, including B lymphocytes, PBMC, immatu re dendritic cells, and mature dendritic cells, Stimulation of protein kina se C activity in APCs significantly enhanced the kinetics of degradation of class II-associated Ii in Ag-processing compartments and the binding of an tigenic peptides to these class II molecules, In cells expressing an Ii-pho sphorylation mutant, trafficking of class II molecules to endosomes was imp aired and Ii proteolysis was inhibited, demonstrating a direct effect of Ii phosphorylation on MHC class II trafficking, These results demonstrate tha t phosphorylation of Ii in APCs alters the kinetics of trafficking of newly synthesized class II molecules to lysosomal Ag-processing compartments.