Identification of antigens presented by MHC for vaccines against tuberculosis
Open accessAbstract
Mycobacterium tuberculosis ( M.tb ) is responsible for more deaths globally than any other pathogen. The only available vaccine, bacillus Calmette-Guérin (BCG), has variable efficacy throughout the world. A more effective vaccine is urgently needed. The immune response against tuberculosis relies, at least in part, on CD4 + T cells. Protective vaccines require the induction of antigen-specific CD4 + T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. In order to identify mycobacterial antigens bound to MHC, we have immunoprecipitated MHC class-I and class-II complexes from THP-1 macrophages infected with BCG, purified MHC class-I and MHC class-II peptides and analysed them by liquid chromatography tandem mass spectrometry. We have successfully identified 94 mycobacterial peptides presented by MHC-II and 43 presented by MHC-I, from 76 and 41 antigens, respectively. These antigens were found to be highly expressed in infected macrophages. Gene ontology analysis suggests most of these antigens are associated with membranes and involved in lipid biosynthesis and transport. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cell from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying new candidate antigens.
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Melanoma cells and antigen-presenting cells can both display HLA-I and HLA-II peptides of bacterial origin.
“We demonstrate that bacterial HLA-I and HLA-II peptides can be presented by both antigen-presenting cells (as has previously been shown25–28) and by melanoma cells”
From Identification of bacteria-derived HLA-bound peptides in melanoma (2021) · cites this paper as [25]
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Identification of bacteria-derived HLA-bound peptides in melanoma
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- Authors
- Bettencourt, P., Müller, J., Nicastri, A., Cantillon, D., Madhavan, M., Charles, P. D., Fotso, C. B., Wittenberg, R., Bull, N., Pinpathomrat, N., Waddell, S. J., Stylianou, E., Hill, A. V. S., Ternette, N., & McShane, H.
- Affiliations
- University of Oxford (GB)
- Brighton and Sussex Medical School (GB)
- Corresponding author
- Bettencourt, Paulo
- ORCID
- Venue
- npj Vaccines
- Published
- 2020-01-03
- Volume
- 5
- Issue
- 1
- Pages
- 2-2
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC6941960
- OpenAlex
- W2996703088
- Cited by
- 110
- References
- 65
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 21 · 2023: 16 · 2022: 15 · 2021: 19 · 2020: 14
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Wellcome Trust (204538/Z/16/Z, 206331/Z/17/Z)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tuberculosis vaccine, Mycobacterium tuberculosis, MHC class I, MHC class II, antigen presentation, CD4+ T cells, BCG, THP-1 macrophages, lipogenesis, immunogenicity
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