title: Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis.
abstract: Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4+ T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp+-compartments. BCG and TB10.4 however, were directed to different types of Lamp+-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. rob@ssi.dk
authors.forename: Rolf
authors.initials: R
authors.lastname: Billeskov
authors.forename: Michael V
authors.initials: MV
authors.lastname: Grandal
authors.forename: Christian
authors.initials: C
authors.lastname: Poulsen
authors.forename: Jan P
authors.initials: JP
authors.lastname: Christensen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winther
authors.forename: Carina
authors.initials: C
authors.lastname: Vingsbo-Lundberg
authors.forename: Truc T K T
authors.initials: TT
authors.lastname: Hoang
authors.forename: Bo
authors.initials: B
authors.lastname: van Deurs
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Song
authors.forename: Claus
authors.initials: C
authors.lastname: Aagaard
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology* / Q000493:pharmacokinetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D003433:Crosses, Genetic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000493:pharmacokinetics; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma