title: A limited antigen-specific cellular response is sufficient for the early control of Mycobacterium tuberculosis in the lung but is insufficient for long-term survival.
abstract: Mice that were transgenic for a T-cell receptor (TCR) specific for ovalbumin peptide(323-339) (DO11.10) were able to survive an infection with Mycobacterium tuberculosis for approximately 80 days. This limited early control of infection was associated with gamma interferon production, inducible nitric oxide synthase expression within the lung, and an influx of clonotypic lymphocytes. The control of M. tuberculosis was lost in DO11.10 mice bred in a rag mutant background, demonstrating that the immune responsiveness was recombinase dependent and likely to be associated with the expression of an alternative alpha TCR by DO11.10 mice. A characterization of the antigen specificity in DO11.10 TCR transgenic mice demonstrated that the specificity was limited and dominated by the 26-kDa (Rv1411c) lipoprotein of M. tuberculosis. This study identifies this lipoprotein as an important and potent inducer of protective T cells within the lungs of mice infected with M. tuberculosis and therefore as a possible target for vaccination.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. turner-11@medctr.osu.edu
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dobos
authors.forename: Marc A
authors.initials: MA
authors.lastname: Keen
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Frank
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002473:Cell Wall / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin