title: The cytoplasmic tail of invariant chain modulates antigen processing and presentation.
abstract: The MHC class II-associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of Iip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and Ii itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distribution in the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an Ii-dependent MHC class II-restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest that this causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the Iip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation.
authors.affiliation: Division of Molecular Cell Biology, Department of Biology, University of Oslo, Oslo, Norway.
authors.forename: Tone F
authors.initials: TF
authors.lastname: Gregers
authors.forename: Tommy W
authors.initials: TW
authors.lastname: Nordeng
authors.forename: Hanne C G
authors.initials: HC
authors.lastname: Birkeland
authors.forename: Inger
authors.initials: I
authors.lastname: Sandlie
authors.forename: Oddmund
authors.initials: O
authors.lastname: Bakke
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001692:Biological Transport; D019556:COS Cells; D019256:Cadmium Chloride / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D002522:Chlorocebus aethiops; D004285:Dogs; D004705:Endocytosis; D010450:Endopeptidases / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D006207:Half-Life; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007668:Kidney; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology; D012276:Ricin / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C045084:invariant chain; D012276:Ricin; D008668:Metallothionein; D010450:Endopeptidases; D019256:Cadmium Chloride