Protein kinase Balpha is required for vesicle trafficking and class II presentation of IgA Fc receptor (CD89)-targeted antigen.
Ag presentation stimulates Ag-specific adaptive immune responses. FcalphaR (CD89)-mediated capture of IgA-bound exogenous Ag leads to efficient MHC class II Ag presentation by APCs. CD89 signaling is required for trafficking of internalized Ag to specialized multivesicular bodies known as MHC class II compartments (MIIC) and subsequent class II presentation. In the present study, we tested the hypothesis that the vesicle trafficking regulator protein kinase Balpha (PKBalpha) is required for CD89-mediated trafficking to MIIC and Ag presentation. We observed by two independent methods (chemical inhibitors and specific RNA interference) that PKBalpha was required for CD89 trafficking to MIIC and class II Ag presentation. Expression of constitutively active PKBalpha in APCs expressing a mutant CD89 accessory signaling molecule (deficient in CD89/Ag trafficking, processing, and presentation) induced trafficking of CD89 to lamp1-containing late endocytic vesicles, but not class II-containing vesicles (MIIC), or class II Ag presentation. These studies show for the first time that PKBalpha is required for receptor-mediated Ag presentation and suggest the mechanism of action includes regulation of vesicle trafficking.
Lang
Gillian A
GA
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03766, USA.
Lang
Mark L
ML
D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D004789:Enzyme Activation; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering; D011961:Receptors, Fc; D051057:Proto-Oncogene Proteins c-akt