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

Giovanni Delogu, S Temmerman, K Pethe, M Parra, S Alonso, C Rouanet, T Pickett, A Drowart, A Debrie, Fd Menozzi, C Sergheraert, Mj Brennan, F Mascart, C. Locht

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

114 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)935-941
Numero di pagine7
RivistaNature Medicine
Volume10
DOI
Stato di pubblicazionePubblicato - 2004

Keywords

  • Animals
  • Bacterial Proteins
  • Belgium
  • Cytotoxicity Tests, Immunologic
  • Female
  • Humans
  • Interferon-gamma
  • Membrane Proteins
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis
  • Protein Processing, Post-Translational
  • T-Lymphocytes
  • Tuberculosis
  • Vaccination

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