Actin microfilaments control the MHC class II antigen presentation pathway in B cells.
Newly synthesised major histocompatibility complex class II molecules associate with invariant chains (Ii) to form nonameric complexes. These complexes are transported to endosomes, where proteolytic enzymes generate alphabeta class II dimers associated with nested Ii-derived peptides. These peptides are then exchanged with antigen peptide, and mature class II molecules reach the cell surface. The role of the actin cytoskeleton in the transport and maturation of class II molecules has not been studied. We show here that upon treatment with cytochalasin D (cyto D), the rate of Ii degradation is drastically reduced in B cells. Cyto D treatment also leads to a delayed appearance of stable forms of class II molecules, and a reduced presentation efficiency of antigen determinants requiring newly synthesised class II molecules. Under such conditions, we found that invariant chain fragments and class II molecules are accumulated in early and late endosomal compartments, whereas the leupeptin protease inhibitor induces their accumulation in lysosomal compartments. The addition of cyto D to leupeptin blocks the delivery of class II/invariant chain complexes to lysosomes, and further inhibits degradation of Ii. The dynamics of the actin cytoskeleton can therefore control the meeting point between newly synthesised class II molecules and lysosomal proteases, involved in Ii degradation and antigen peptide loading.
Barois
N
N
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Forquet
F
F
Davoust
J
J
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport / Q000276:immunology; D002451:Cell Compartmentation / Q000276:immunology; D015638:Cytochalasin D / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000199:Actins; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D011947:Receptors, Antigen, B-Cell; C045084:invariant chain; D015638:Cytochalasin D