title: Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+T Cells.
abstract: Tuberculosis (TB) due toMycobacterium tuberculosisremains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. We previously reported that a genetically modified strain ofMycobacterium smegmatiscalled IKEPLUS is a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4+T cell memory, we hypothesized that the specificity of the CD4+T cell response was a critical feature of this protection. Usingin vitroassays of interferon gamma production (enzyme-linked immunosorbent spot [ELISPOT] assays) by splenocytes from IKEPLUS-immunized C57BL/6J mice, we identified an immunogenic peptide within the mycobacterial ribosomal large subunit protein RplJ, encoded by the Rv0651 gene. In a complementary approach, we generated major histocompatibility complex (MHC) class II-restricted T cell hybridomas from IKEPLUS-immunized mice. Screening of these T cell hybridomas against IKEPLUS and ribosomes enriched from IKEPLUS suggested that the CD4+T cell response in IKEPLUS-immunized mice was dominated by the recognition of multiple components of the mycobacterial ribosome. Importantly, CD4+T cells specific for mycobacterial ribosomes accumulate to significant levels in the lungs of IKEPLUS-immunized mice following aerosol challenge with virulentM. tuberculosis, consistent with a role for these T cells in protective host immunity in TB. The identification of CD4+T cell responses to defined ribosomal protein epitopes expands the range of antigenic targets for adaptive immune responses toM. tuberculosisand may help to inform the design of more effective vaccines against tuberculosis.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Johnson
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Kennedy
authors.affiliation: Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Lindestam Arlehamn
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Goldberg
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Saini
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Sinu
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Subray S
authors.initials: SS
authors.lastname: Hegde
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Blanchard
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.|Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.affiliation: Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA steven.porcelli@einstein.yu.edu.|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007114:Immunization; D051379:Mice; D009161:Mycobacterium / Q000276:immunology* / Q000472:pathogenicity; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D012269:Ribosomal Proteins
keywords: T cells; antigen; epitope; ribosome; tuberculosis