title: Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments.
abstract: Virions of filamentous bacteriophage fd are capable of displaying multiple copies of peptide epitopes and generating powerful immune responses to them. To investigate the antigen processing mechanisms in human B cell lines used as antigen presenting cells, the major coat protein (pVIII) in intact virions was fluorescently labeled, and its localization in various intracellular compartments was followed using confocal microscopy. We show that the virions were taken up and processed to yield peptides that reach both the major histocompatibility complex (MHC) class II compartment and the endoplasmic reticulum. Moreover, when exposed to bacteriophages displaying a cytotoxic T lymphocyte (CTL) epitope from the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1), B cells were lysed by specific cytotoxic lymphocytes. This confirms that filamentous bacteriophage virions are capable of being taken up and processed efficiently by MHC class I and class II pathways, even in nonprofessional antigen presenting cells. These remarkable features explain, at least in part, the unexpected ability of virions displaying foreign T-cell epitopes to prime strong T-helper-dependent CTL responses. These findings have important implications for the development of peptide-based vaccines, using filamentous bacteriophage virions as scaffolds.
authors.affiliation: Génomique Fonctionnelle et Biologie Systémique en Santé, Centre National de la Recherche Scientifique, Villejuif, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Gaubin
authors.forename: Cristina
authors.initials: C
authors.lastname: Fanutti
authors.forename: Zohar
authors.initials: Z
authors.lastname: Mishal
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
authors.forename: Rossella
authors.initials: R
authors.lastname: Sartorius
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
authors.forename: John
authors.initials: J
authors.lastname: Guardiola
authors.forename: Richard N
authors.initials: RN
authors.lastname: Perham
authors.forename: Dominique
authors.initials: D
authors.lastname: Piatier-Tonneau
mesh_terms: D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017104:Bacteriophage M13 / Q000276:immunology / Q000502:physiology*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016650:Fluorescein-5-isothiocyanate