title: BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs.
abstract: A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis-infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies.
authors.affiliation: Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany;
authors.forename: Eva
authors.initials: E
authors.lastname: Kaufmann
authors.affiliation: Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Spohr
authors.affiliation: Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany;
authors.forename: Sibylle
authors.initials: S
authors.lastname: Battenfeld
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France;
authors.forename: Diane
authors.identifier: http://orcid.org/0000-0002-9421-8515
authors.initials: D
authors.lastname: De Paepe
authors.affiliation: Division of Allergology, Paul-Ehrlich-Institut, 63225 Langen, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Holzhauser
authors.affiliation: Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Balks
authors.affiliation: Forschungszentrum Borstel, 23845 Borstel, Germany; and.
authors.forename: Susanne
authors.initials: S
authors.lastname: Homolka
authors.affiliation: Forschungszentrum Borstel, 23845 Borstel, Germany; and.
authors.forename: Norbert
authors.identifier: http://orcid.org/0000-0001-6673-4291
authors.initials: N
authors.lastname: Reiling
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France;
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.affiliation: Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany; Friedrich-Loeffler-Institut, 17893 Greifswald-Insel Riems, Germany max.bastian@fli.bund.de.
authors.forename: Max
authors.identifier: http://orcid.org/0000-0002-2581-3302
authors.initials: M
authors.lastname: Bastian
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006168:Guinea Pigs; D054884:Host-Pathogen Interactions; D006801:Humans; D055666:Lipopeptides / Q000276:immunology; D008213:Lymphocyte Activation; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001426:Bacterial Proteins; D055666:Lipopeptides; D014373:Tuberculin