1. Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin.
- Author
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Temmerman S, Pethe K, Parra M, Alonso S, Rouanet C, Pickett T, Drowart A, Debrie AS, Delogu G, Menozzi FD, Sergheraert C, Brennan MJ, Mascart F, and Locht C
- Subjects
- Animals, Bacterial Proteins immunology, Belgium, Cytotoxicity Tests, Immunologic, Female, Humans, Interferon-gamma metabolism, Membrane Proteins immunology, Methylation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Tuberculosis prevention & control, Bacterial Proteins metabolism, Membrane Proteins metabolism, Mycobacterium tuberculosis metabolism, Protein Processing, Post-Translational immunology, T-Lymphocytes immunology, Tuberculosis immunology, Vaccination
- Abstract
Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA) by the bacterium is essential for effective T cell immunity to this antigen in infected healthy humans and in mice. Methylated HBHA provides high levels of protection against M. tuberculosis challenge in mice, whereas nonmethylated HBHA does not. Protective immunity induced by methylated HBHA is comparable to that afforded by vaccination with bacille Calmette et Guérin, the only available anti-tuberculosis vaccine. Thus, post-translational modifications of proteins may be crucial for their ability to induce protective T cell-mediated immunity against infectious diseases such as tuberculosis.
- Published
- 2004
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