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Article
Nature Medicine  10, 935 - 941 (2004)
Published online: 8 August 2004; | doi:10.1038/nm1090

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

Stéphane Temmerman1, 7, Kevin Pethe2, 6, 7, Marcela Parra3, Sylvie Alonso2, 6, Carine Rouanet2, Thames Pickett3, Annie Drowart4, Anne-Sophie Debrie2, Giovanni Delogu3, 6, Franco D Menozzi2, Christian Sergheraert5, Michael J Brennan3, Françoise Mascart1 & Camille Locht2

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

2  Unité INSERM U629, IBL, Institut Pasteur de Lille, 1, Rue du Professor Calmette, F-59019 Lille Cedex, France.

3  Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.

4  Department of Internal Medicine, Brugmann Hospital, Place Van Gehuchten, 4, B-1020 Brussels, Belgium.

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

6  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.).

7  These authors contributed equally to this work.

Correspondence should be addressed to Camille Locht camille.locht@pasteur-lille.fr
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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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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