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

Authors

• Sudhasini Panda, La Jolla Institute for Immunology
• Jeffrey Morgan, La Jolla Institute for Immunology
• Catherine Cheng, La Jolla Institute for Immunology
• Mayuko Saito, Tohoku University Graduate School of Medicine, Sendai, Japan
• Robert H. Gilman, Universidad Peruana Cayetano Heredia, Lima, Peru
• Nelly Ciobanu, Phthisiopneumology Institute, Chisinau, Republic of Moldova
• Valeriu Crudu, Phthisiopneumology Institute, Chisinau, Republic of Moldova
• Donald G. Cantazaro, University of Arkansas, Fayetteville
• Antonino Cantazaro, University of California San Diego, La Jolla, CA
• Timothy Rodwell, University of California San Diego, La Jolla, CA
• Judy S.B. Perera, General Sir John Kotelawala Defense University, Ratmalana, Sri Lanka
• Teshan Chathuranga, General Sir John Kotelawala Defense University, Ratmalana, Sri Lanka
• Bandu Gunasena, National Hospital for Respiratory Diseases, Welisara, Sri Lanka
• Aruna D. DeSilva, La Jolla Institute for Immunology, La Jolla, CA
• Bjoern Peters, La Jolla Institute for Immunology, La Jolla, CA
• Alessandro Sette, La Jolla Institute for Immunology, La Jolla, CA
• Cecilia S. Linderstam Arlehamn, La Jolla Institute for Immunology, La Jolla, CA

Document Type

Article

Publication Date

1-26-2024

Keywords

tuberculosis, T cell, immune response

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 + /− indi- viduals 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

Citation

Panda, S., Morgan, J., Cheng, C. et al. Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection. Nat Commun 15, 765 (2024). https://doi.org/10.1038/s41467-024-45058-9

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.