Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin.
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.
Temmerman
Stéphane
S
Laboratory of Immunology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808, B-1070 Brussels, Belgium.
Pethe
Kevin
K
Parra
Marcela
M
Alonso
Sylvie
S
Rouanet
Carine
C
Pickett
Thames
T
Drowart
Annie
A
Debrie
Anne-Sophie
AS
Delogu
Giovanni
G
Menozzi
Franco D
FD
Sergheraert
Christian
C
Brennan
Michael J
MJ
Mascart
Françoise
F
Locht
Camille
C
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D001530:Belgium; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination
D001426:Bacterial Proteins; C440647:HbhA protein, Mycobacterium tuberculosis; D008565:Membrane Proteins; D007371:Interferon-gamma