Selective modulation of the major histocompatibility complex class II antigen presentation pathway following B cell receptor ligation and protein kinase C activation.
We noticed that B cell receptor ligation or phorbol 12-myristate 13-acetate treatment induced intracellular vesicles containing major histocompatibility complex (MHC) class II and invariant chain (Ii), and increased the amount of transmembrane p12 Ii fragments coimmunoprecipitated with class II molecules. To determine the influence of protein kinase C activation on the MHC class II presentation pathway, we analyzed the subcellular distribution of Ii, the induction of SDS-stable forms of class II molecules, and their ability to present different antigens. Ii chains visualized with luminal and cytoplasmic directed antibodies appeared in early endosomal compartments accessible to transferrin in response to phorbol 12-myristate 13-acetate treatment, whereas transmembrane Ii degradation products equivalent to the p12 Ii fragments were colocalized with the B cell receptors internalized after cross-linking. Protein kinase C activation delayed in parallel the formation of SDS-stable forms of class II molecules and reduced the presentation of antigenic determinants requiring newly synthesized class II alphabeta-Ii complexes. These data indicate that B cell activation affects Ii processing and MHC class II peptide loading in endosomal compartments intersecting the biosynthetic pathway.
Barois
N
N
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, 13, 288 Marseille, France.
Forquet
F
F
Davoust
J
J
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; C045084:invariant chain; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate