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Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin

Nature Medicine volume 10, pages 935941 (2004) | Download Citation

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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.

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Acknowledgements

We thank F. Biet for help with immunization and challenge experiments, J.P. Decavel for help with mouse handling, E. Willery for help with ELISA and A. Capron and D.G. Russell for critically reading the manuscript. This work was supported by INSERM, Institut Pasteur de Lille, Région Nord-Pas de Calais, the Ministère de la Recherche, the Fond National de la Recherche Scientifique Médicale, the Centre de la Recherche Interuniversitaire en Vaccinologie and a grant from GlaxoSmithKline, Belgium. K.P. was supported by a fellowship from the Ministère de la Recherche and la Fondation pour la Recherche Médicale; S.T. by la Fondation pour la Formation à la Recherche dans l'Industrie et l'Agriculture; S.A. by Aventis-Pasteur; G. D. by Areas Global TB Vaccine Foundation; and M.J.B. by a grant from the US National Vaccine Program Office.

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Author notes

    • Kevin Pethe
    • , Sylvie Alonso
    •  & Giovanni Delogu

    Present addresses: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA (K.P. and S.A.); Institute of Microbiology, Catholic University of the Sacred Heart, Rome, Italy (G.D.).

    • Stéphane Temmerman
    •  & Kevin Pethe

    These authors contributed equally to this work.

Affiliations

  1. Laboratory of Immunology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808, B-1070 Brussels, Belgium.

    • Stéphane Temmerman
    •  & Françoise Mascart
  2. Unité INSERM U629, IBL, Institut Pasteur de Lille, 1, Rue du Professor Calmette, F-59019 Lille Cedex, France.

    • Kevin Pethe
    • , Sylvie Alonso
    • , Carine Rouanet
    • , Anne-Sophie Debrie
    • , Franco D Menozzi
    •  & Camille Locht
  3. Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.

    • Marcela Parra
    • , Thames Pickett
    • , Giovanni Delogu
    •  & Michael J Brennan
  4. Department of Internal Medicine, Brugmann Hospital, Place Van Gehuchten, 4, B-1020 Brussels, Belgium.

    • Annie Drowart
  5. CNRS-Université Lille 2 UMR8525, IBL, Institut Pasteur de Lille, 1, rue du Prof. Calmette, F-59019 Lille Cedex, France.

    • Christian Sergheraert

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Camille Locht.

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DOI

https://doi.org/10.1038/nm1090