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Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection

Author

Listed:
  • Sudhasini Panda

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology)

  • Jeffrey Morgan

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology)

  • Catherine Cheng

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology)

  • Mayuko Saito

    (Tohoku University Graduate School of Medicine)

  • Robert H. Gilman

    (Johns Hopkins School of Public Health
    Universidad Peruana Cayetano Heredia)

  • Nelly Ciobanu

    (Phthisiopneumology Institute)

  • Valeriu Crudu

    (Phthisiopneumology Institute)

  • Donald G. Catanzaro

    (University of Arkansas)

  • Antonino Catanzaro

    (University of California San Diego)

  • Timothy Rodwell

    (University of California San Diego)

  • Judy S. B. Perera

    (General Sir John Kotelawala Defense University)

  • Teshan Chathuranga

    (General Sir John Kotelawala Defense University)

  • Bandu Gunasena

    (National Hospital for Respiratory Diseases)

  • Aruna D. DeSilva

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
    General Sir John Kotelawala Defense University)

  • Bjoern Peters

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
    University of California San Diego)

  • Alessandro Sette

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
    University of California San Diego)

  • Cecilia S. Lindestam Arlehamn

    (Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology)

Abstract

There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /−) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /− individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses.

Suggested Citation

  • Sudhasini Panda & Jeffrey Morgan & Catherine Cheng & Mayuko Saito & Robert H. Gilman & Nelly Ciobanu & Valeriu Crudu & Donald G. Catanzaro & Antonino Catanzaro & Timothy Rodwell & Judy S. B. Perera & , 2024. "Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45058-9
    DOI: 10.1038/s41467-024-45058-9
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    References listed on IDEAS

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    1. Joshua S. Woodworth & Helena Strand Clemmensen & Hannah Battey & Karin Dijkman & Thomas Lindenstrøm & Raquel Salvador Laureano & Randy Taplitz & Jeffrey Morgan & Claus Aagaard & Ida Rosenkrands & Ceci, 2021. "A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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