Identification of mycobacterial RplJ/L10 and RpsA/S1 proteins as novel targets for CD4+ T cells

Alison J. Johnson, Steven C. Kennedy, Cecilia S Lindestam Arlehamn, Michael F. Goldberg, Neeraj K. Saini, Jiayong Xu, Sinu Paul, Subray S. Hegde, John S. Blanchard, John Chan, William R. Jacobs, Alessandro Sette, Steven A. Porcelli

Research output: Contribution to journalArticle

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Abstract

Tuberculosis (TB) due to Mycobacterium tuberculosis remains 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 of Mycobacterium smegmatis called 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. Using in vitro assays 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 IKEPLUSimmunized mice following aerosol challenge with virulent M. 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 to M. tuberculosis and may help to inform the design of more effective vaccines against tuberculosis.

Original languageEnglish (US)
Article numbere01023-16
JournalInfection and Immunity
Volume85
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

T-Lymphocytes
Ribosomes
Mycobacterium tuberculosis
Tuberculosis Vaccines
Proteins
Hybridomas
Immunity
Tuberculosis
Large Ribosome Subunits
T-Cell Antigen Receptor Specificity
Mycobacterium smegmatis
CD4 Antigens
Ribosomal Proteins
Adaptive Immunity
Major Histocompatibility Complex
Aerosols
Inbred C57BL Mouse
Interferon-gamma
Communicable Diseases
Epitopes

Keywords

  • Antigen
  • Epitope
  • Ribosome
  • T cells
  • Tuberculosis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Johnson, A. J., Kennedy, S. C., Arlehamn, C. S. L., Goldberg, M. F., Saini, N. K., Xu, J., ... Porcelli, S. A. (2017). Identification of mycobacterial RplJ/L10 and RpsA/S1 proteins as novel targets for CD4+ T cells. Infection and Immunity, 85(4), [e01023-16]. https://doi.org/10.1128/IAI.01023-16

Identification of mycobacterial RplJ/L10 and RpsA/S1 proteins as novel targets for CD4+ T cells. / Johnson, Alison J.; Kennedy, Steven C.; Arlehamn, Cecilia S Lindestam; Goldberg, Michael F.; Saini, Neeraj K.; Xu, Jiayong; Paul, Sinu; Hegde, Subray S.; Blanchard, John S.; Chan, John; Jacobs, William R.; Sette, Alessandro; Porcelli, Steven A.

In: Infection and Immunity, Vol. 85, No. 4, e01023-16, 01.04.2017.

Research output: Contribution to journalArticle

Johnson AJ, Kennedy SC, Arlehamn CSL, Goldberg MF, Saini NK, Xu J et al. Identification of mycobacterial RplJ/L10 and RpsA/S1 proteins as novel targets for CD4+ T cells. Infection and Immunity. 2017 Apr 1;85(4). e01023-16. https://doi.org/10.1128/IAI.01023-16
Johnson, Alison J. ; Kennedy, Steven C. ; Arlehamn, Cecilia S Lindestam ; Goldberg, Michael F. ; Saini, Neeraj K. ; Xu, Jiayong ; Paul, Sinu ; Hegde, Subray S. ; Blanchard, John S. ; Chan, John ; Jacobs, William R. ; Sette, Alessandro ; Porcelli, Steven A. / Identification of mycobacterial RplJ/L10 and RpsA/S1 proteins as novel targets for CD4+ T cells. In: Infection and Immunity. 2017 ; Vol. 85, No. 4.
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abstract = "Tuberculosis (TB) due to Mycobacterium tuberculosis remains 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 of Mycobacterium smegmatis called 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. Using in vitro assays 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 IKEPLUSimmunized mice following aerosol challenge with virulent M. 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 to M. tuberculosis and may help to inform the design of more effective vaccines against tuberculosis.",
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AU - Xu, Jiayong

AU - Paul, Sinu

AU - Hegde, Subray S.

AU - Blanchard, John S.

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