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Clinical Research and Public HealthIn-Press PreviewImmunologyInfectious diseaseMicrobiology Open Access | 10.1172/jci.insight.202134

Rare variable M. tuberculosis antigens induce predominant Th17 responses in human infection

Paul Ogongo,1 Liya Wassie,2 Anthony Tran,1 Devin Columbus,1 Julia Huffaker,1 Lisa Sharling,3 Gregory Ouma,4 Samuel Gurrion Ouma,4 Kidist Bobosha,2 Cecilia S. Lindestam Arlehamn,5 Neel R. Gandhi,3 Sara C. Auld,3 Jyothi Rengarajan,6 Cheryl L. Day,7 Artur Queiroz,8 Mariana Araújo-Pereira,8 Eduardo Fukutani,8 Bruno B. Andrade,8 John D. Altman,7 Henry M. Blumberg,3 and Joel D. Ernst1

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Ogongo, P. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Wassie, L. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Tran, A. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Columbus, D. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Huffaker, J. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Sharling, L. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Ouma, G. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Ouma, S. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Bobosha, K. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Lindestam Arlehamn, C. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Gandhi, N. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Auld, S. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Rengarajan, J. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Day, C. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Queiroz, A. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Araújo-Pereira, M. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Fukutani, E. in: PubMed | Google Scholar

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Andrade, B. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Altman, J. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Blumberg, H. in: PubMed | Google Scholar |

1Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States of America

2Mycobacterial Disease Research Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia

3Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, United States of America

4Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

5Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, United States of America

6Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, United States of America

7Emory Vaccine Center, Emory University, Atlanta, United States of America

8Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil

Find articles by Ernst, J. in: PubMed | Google Scholar |

Published January 27, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.202134.
Copyright © 2026, Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 27, 2026 - Version history
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Abstract

CD4 T cells are essential for immunity to M. tuberculosis (Mtb), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity to Mtb. While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that, as in other pathogens, effective immune recognition drives sequence diversity in individual Mtb antigens. We previously identified Mtb genes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in two distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoRγt and produce IL-17, in contrast to ‘classical’ Mtb antigens that induce T cells that produce IFNγ. Together with emerging evidence showing human Th17 responses are associated with prevention of progression to TB disease, our results suggest that RVMA can be valuable antigens in vaccines for those already infected with Mtb to amplify existing antigen-specific Th17 responses to prevent TB disease.

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  • Version 1 (January 27, 2026): In-Press Preview
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