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.
Laboratory of Immunology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808, B-1070 Brussels, Belgium.
Stéphane
S
Temmerman
Kevin
K
Pethe
Marcela
M
Parra
Sylvie
S
Alonso
Carine
C
Rouanet
Thames
T
Pickett
Annie
A
Drowart
Anne-Sophie
AS
Debrie
Giovanni
G
Delogu
Franco D
FD
Menozzi
Christian
C
Sergheraert
Michael J
MJ
Brennan
Françoise
F
Mascart
Camille
C
Locht
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