Invariant chain cleavage and peptide loading in major histocompatibility complex class II vesicles

doi:10.1084/jem.181.5.1729

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Invariant chain cleavage and peptide loading in major histocompatibility complex class II vesicles

S Amigorena, P Webster, J Drake, J Newcomb, P Cresswell and I Mellman
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA.

B lymphocytes contain a novel population of endocytic vesicles involved in the transport of newly synthesized major histocompatibility complex (MHC) class II alpha beta chains and alpha beta peptide complexes to the cell surface. We now present evidence that these class II-enriched vesicles (CIIV) are also likely to be a site for the loading of immunogenic peptides onto MHC molecules. We used the serine protease inhibitor leupeptin to accumulate naturally occurring intermediates in the degradation of alpha beta-invariant chain complexes and to slow the intracellular transport of class II molecules. As expected, leupeptin caused an accumulation of Ii chain and class II molecules (I-A(d)) in endosomes and lysosomes. More importantly, however, it enhanced the selective accumulation of a 10-kD invariant chain fragment associated with sodium dodecyl sulfate (SDS)-labile (empty) alpha beta dimers in CIIV. This was followed by the dissociation of the 10-kD fragment, formation of SDS-stable (peptide-loaded) alpha beta dimers, and their subsequent appearance at the cell surface. Thus, CIIV are likely to serve as a specialized site, distinct from endosomes and lysosomes, that hosts the final steps in the dissociation of invariant chain from class II molecules and the loading of antigen-derived peptides onto newly synthesized alpha beta dimers.
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Neumann, J., Koch, N. (2006). A novel domain on HLA-DR{beta} chain regulates the chaperone role of the invariant chain. J. Cell Sci. 119: 4207-4214 [Abstract] [Full Text]
Liang, F., Seyrantepe, V., Landry, K., Ahmad, R., Ahmad, A., Stamatos, N. M., Pshezhetsky, A. V. (2006). Monocyte Differentiation Up-regulates the Expression of the Lysosomal Sialidase, Neu1, and Triggers Its Targeting to the Plasma Membrane via Major Histocompatibility Complex Class II-positive Compartments. J. Biol. Chem. 281: 27526-27538 [Abstract] [Full Text]
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McCormick, P. J., Martina, J. A., Bonifacino, J. S. (2005). Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proc. Natl. Acad. Sci. USA 102: 7910-7915 [Abstract] [Full Text]
Karacsonyi, C., Knorr, R., Fulbier, A., Lindner, R. (2004). Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading. J. Biol. Chem. 279: 34818-34826 [Abstract] [Full Text]
Lautwein, A., Kraus, M., Reich, M., Burster, T., Brandenburg, J., Overkleeft, H. S., Schwarz, G., Kammer, W., Weber, E., Kalbacher, H., Nordheim, A., Driessen, C. (2004). Human B lymphoblastoid cells contain distinct patterns of cathepsin activity in endocytic compartments and regulate MHC class II transport in a cathepsin S-independent manner. J. Leukoc. Biol. 75: 844-855 [Abstract] [Full Text]
Palliser, D., Ploegh, H., Boes, M. (2004). Myeloid Differentiation Factor 88 Is Required for Cross-Priming In Vivo. J. Immunol. 172: 3415-3421 [Abstract] [Full Text]
Perrin-Cocon, L. A., Villiers, C. L., Salamero, J., Gabert, F., Marche, P. N. (2004). B Cell Receptors and Complement Receptors Target the Antigen to Distinct Intracellular Compartments. J. Immunol. 172: 3564-3572 [Abstract] [Full Text]
El-Sukkari, D., Wilson, N. S., Hakansson, K., Steptoe, R. J., Grubb, A., Shortman, K., Villadangos, J. A. (2003). The Protease Inhibitor Cystatin C Is Differentially Expressed among Dendritic Cell Populations, but Does Not Control Antigen Presentation. J. Immunol. 171: 5003-5011 [Abstract] [Full Text]
Lennon-Dumenil, A.-M., Bakker, A. H., Maehr, R., Fiebiger, E., Overkleeft, H. S., Rosemblatt, M., Ploegh, H. L., Lagaudriere-Gesbert, C. (2002). Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation. JEM 196: 529-540 [Abstract] [Full Text]
Cebulla, C. M., Miller, D. M., Zhang, Y., Rahill, B. M., Zimmerman, P., Robinson, J. M., Sedmak, D. D. (2002). Human Cytomegalovirus Disrupts Constitutive MHC Class II Expression. J. Immunol. 169: 167-176 [Abstract] [Full Text]
Nordeng, T. W., Gregers, T. F., Kongsvik, T. L., Meresse, S., Gorvel, J.-P., Jourdan, F., Motta, A., Bakke, O. (2002). The Cytoplasmic Tail of Invariant Chain Regulates Endosome Fusion and Morphology. Mol. Biol. Cell 13: 1846-1856 [Abstract] [Full Text]
Benharouga, M., Haardt, M., Kartner, N., Lukacs, G. L. (2001). Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments. JCB 153: 957-970 [Abstract] [Full Text]
Haque, M. A., Hawes, J. W., Blum, J. S. (2001). Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition. J. Immunol. 166: 4543-4551 [Abstract] [Full Text]
Vincent-Schneider, H, Thery, C, Mazzeo, D, Tenza, D, Raposo, G, Bonnerot, C (2001). Secretory granules of mast cells accumulate mature and immature MHC class II molecules. J. Cell Sci. 114: 323-334 [Abstract]
Ramachandra, L., Harding, C. V. (2000). Phagosomes Acquire Nascent and Recycling Class II MHC Molecules but Primarily Use Nascent Molecules in Phagocytic Antigen Processing. J. Immunol. 164: 5103-5112 [Abstract] [Full Text]
Denzer, K, Kleijmeer, M., Heijnen, H., Stoorvogel, W, Geuze, H. (2000). Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 113: 3365-3374 [Abstract]
Ramm, G, Pond, L, Watts, C, Stoorvogel, W (2000). Clathrin-coated lattices and buds on MHC class II compartments do not selectively recruit mature MHC-II. J. Cell Sci. 113: 303-313 [Abstract]
Driessen, C., Bryant, R. A.R., Lennon-Dumenil, A.-M., Villadangos, J. A., Bryant, P. W., Shi, G.-P., Chapman, H. A., Ploegh, H. L. (1999). Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells. JCB 147: 775-790 [Abstract] [Full Text]
Ashman, J. B., Miller, J. (1999). A Role for the Transmembrane Domain in the Trimerization of the MHC Class II-Associated Invariant Chain. J. Immunol. 163: 2704-2712 [Abstract] [Full Text]
Ramachandra, L., Song, R., Harding, C. V. (1999). Phagosomes Are Fully Competent Antigen-Processing Organelles That Mediate the Formation of Peptide:Class II MHC Complexes. J. Immunol. 162: 3263-3272 [Abstract] [Full Text]
Natarajan, S. K., Stern, L. J., Sadegh-Nasseri, S. (1999). Sodium Dodecyl Sulfate Stability of HLA-DR1 Complexes Correlates with Burial of Hydrophobic Residues in Pocket 1. J. Immunol. 162: 3463-3470 [Abstract] [Full Text]
Drake, J. R., Lewis, T. A., Condon, K. B., Mitchell, R. N., Webster, P. (1999). Involvement of MIIC-Like Late Endosomes in B Cell Receptor-Mediated Antigen Processing in Murine B Cells. J. Immunol. 162: 1150-1155 [Abstract] [Full Text]
Antoine, J., Lang, T, Prina, E, Courret, N, Hellio, R (1999). H-2M molecules, like MHC class II molecules, are targeted to parasitophorous vacuoles of Leishmania-infected macrophages and internalized by amastigotes of L. amazonensis and L. mexicana. J. Cell Sci. 112: 2559-2570 [Abstract]
Ceman, S., Wu, S., Jardetzky, T. S., Sant, A. J. (1998). Alteration of a Single Hydrogen Bond between Class II Molecules and Peptide Results in Rapid Degradation of Class II Molecules after Invariant Chain Removal. JEM 188: 2139-2149 [Abstract] [Full Text]
Thery, C., Brachet, V., Regnault, A., Rescigno, M., Ricciardi-Castagnoli, P., Bonnerot, C., Amigorena, S. (1998). MHC Class II Transport from Lysosomal Compartments to the Cell Surface Is Determined by Stable Peptide Binding, But Not by the Cytosolic Domains of the {alpha}- and {beta}-Chains. J. Immunol. 161: 2106-2113 [Abstract] [Full Text]
Schafer, P. H., Malapati, S., Hanfelt, K. K., Pierce, S. K. (1998). The Assembly and Stability of MHC Class II-({alpha}{beta})2 Superdimers. J. Immunol. 161: 2307-2316 [Abstract] [Full Text]
Faigle, W., Raposo, G., Tenza, D., Pinet, V., Vogt, A. B., Kropshofer, H., Fischer, A., de Saint-Basile, G., Amigorena, S. (1998). Deficient Peptide Loading and MHC Class II Endosomal Sorting in a Human Genetic Immunodeficiency Disease: the Chediak-Higashi Syndrome. JCB 141: 1121-1134 [Abstract] [Full Text]
Barlow, A. K., He, X., Janeway, C. Jr. (1998). Exogenously Provided Peptides of a Self-antigen Can Be Processed into Forms that Are Recognized by Self-T Cells. JEM 187: 1403-1415 [Abstract] [Full Text]
Deussing, J., Roth, W., Saftig, P., Peters, C., Ploegh, H. L., Villadangos, J. A. (1998). Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc. Natl. Acad. Sci. USA 95: 4516-4521 [Abstract] [Full Text]
Bikoff, E. K., Kenty, G., Van Kaer, L. (1998). Distinct Peptide Loading Pathways for MHC Class II Molecules Associated with Alternative Ii Chain Isoforms. J. Immunol. 160: 3101-3110 [Abstract] [Full Text]
Amigorena, S., Lankar, D., Briken, V., Gapin, L., Viguier, M., Bonnerot, C. (1998). Type II and III Receptors for Immunoglobulin G (IgG) Control the Presentation of Different T Cell Epitopes from Single IgG-complexed Antigens. JEM 187: 505-515 [Abstract] [Full Text]
Barois, N, Forquet, F, Davoust, J (1998). Actin microfilaments control the MHC class II antigen presentation pathway in B cells. J. Cell Sci. 111: 1791-1800 [Abstract]
Wolins, N., Bosshart, H., Kuster, H., Bonifacino, J. S. (1997). Aggregation As a Determinant of Protein Fate in Post-Golgi Compartments: Role of the Luminal Domain of Furin in Lysosomal Targeting. JCB 139: 1735-1745 [Abstract] [Full Text]
Ferrari, G., Knight, A. M., Watts, C., Pieters, J. (1997). Distinct Intracellular Compartments Involved in Invariant Chain Degradation and Antigenic Peptide Loading of Major Histocompatibility Complex (MHC) Class II Molecules. JCB 139: 1433-1446 [Abstract] [Full Text]
Kleijmeer, M. J., Morkowski, S., Griffith, J. M., Rudensky, A. Y., Geuze, H. J. (1997). Major Histocompatibility Complex Class II Compartments in Human and Mouse B Lymphoblasts Represent Conventional Endocytic Compartments. JCB 139: 639-649 [Abstract] [Full Text]
Drake, J. R., Webster, P., Cambier, J. C., Mellman, I. (1997). Delivery of B Cell Receptor-internalized Antigen to Endosomes and Class II Vesicles. JEM 186: 1299-1306 [Abstract] [Full Text]
Villadangos, J. A., Riese, R. J., Peters, C., Chapman, H. A., Ploegh, H. L. (1997). Degradation of Mouse Invariant Chain: Roles of Cathepsins S and D and the Influence of Major Histocompatibility Complex Polymorphism. JEM 186: 549-560 [Abstract] [Full Text]
Brachet, V., Raposo, G., Amigorena, S., Mellman, I. (1997). Ii Chain Controls the Transport of Major Histocompatibility Complex Class II Molecules to and from Lysosomes. JCB 137: 51-65 [Abstract] [Full Text]
Gedde-Dahl, M., Freisewinkel, I., Staschewski, M., Schenck, K., Koch, N., Bakke, O. (1997). Exon 6Is Essential for Invariant Chain Trimerization and Induction of Large Endosomal Structures. J. Biol. Chem. 272: 8281-8287 [Abstract] [Full Text]
Barois, N., Forquet, F., Davoust, J. (1997). Selective Modulation of the Major Histocompatibility Complex Class II Antigen Presentation Pathway following B Cell Receptor Ligation and Protein Kinase C Activation. J. Biol. Chem. 272: 3641-3647 [Abstract] [Full Text]
Escola, J.-M., Deleuil, F., Stang, E., Boretto, J., Chavrier, P., Gorvel, J.-P. (1996). Characterization of a Lysozyme-Major Histocompatibility Complex Class II Molecule-loading Compartment as a Specialized Recycling Endosome in Murine B Lymphocytes. J. Biol. Chem. 271: 27360-27365 [Abstract] [Full Text]
Neumann, J., Schach, N., Koch, N. (2001). Glycosylation Signals That Separate the Trimerization from the MHC Class II-binding Domain Control Intracellular Degradation of Invariant Chain. J. Biol. Chem. 276: 13469-13475 [Abstract] [Full Text]