title: Contrasting efficacy of presentation by major histocompatibility complex class I and class II products when peptides are administered within a common protein carrier, self immunoglobulin.
abstract: Major histocompatibility complex (MHC) class I and II products are specialized to present antigens via different intracellular processing routes. Peptides originating from proteins in the cytoplasm can gain access to class I peptide-binding grooves, most likely in the rough endoplasmic reticulum. Peptides from proteins in acidic endocytic vacuoles gain access to class II. It has been proposed that MHC class I products also can capture peptides from "exogenous" or noninfectious sources, and this assumption underlies the use of intact proteins as vaccines for CD8+ cytotoxic T lymphocytes. Here we describe quantitative information comparing the efficacy of peptide presentation from exogenous proteins by administering a class I- and II-restricted peptide within the same context, the CDR3 loop of the VH domain of a self immunoglobulin. Antigen-presenting cells (APC), including primary dendritic cells, efficiently present an influenza hemagglutinin peptide from the immunoglobulin (Ig) carrier (50% maximal response at 10 nM Ig-HA) to an MHC class II-restricted T cell. In contrast, these same APC are unable to present an influenza nucleoprotein (NP) peptide from the same context (1 microM Ig-NP) to an MHC class I-restricted T cell. Ig-NP DNA transfectants do present the nucleoprotein viral peptide on class I. Thus, peptides within the complementarity-determining region loops of Ig carriers can be presented on class I or II MHC products, but the endocytic compartment, when offered MHC class I- and II-restricted peptides within the same carrier protein context, favors presentation by class II by at least 1000-fold.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: H
authors.initials: H
authors.lastname: Zaghouani
authors.forename: Y
authors.initials: Y
authors.lastname: Kuzu
authors.forename: H
authors.initials: H
authors.lastname: Kuzu
authors.forename: T D
authors.initials: TD
authors.lastname: Brumeanu
authors.forename: W J
authors.initials: WJ
authors.lastname: Swiggard
authors.forename: R M
authors.initials: RM
authors.lastname: Steinman
authors.forename: C A
authors.initials: CA
authors.lastname: Bona
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016601:RNA-Binding Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins