The antituberculous Mycobacterium bovis BCG vaccine is an attenuated mycobacterial producer of phosphorylated nonpeptidic antigens for human gamma delta T cells

Abstract

The mycobacterial antigens stimulating human gamma delta T lymphocytes (R. L. Modlin, C. Permitz, F. M. Hofman, V. Torigian, K. Uemura, T. H. Rea, B. R. Bloom, and M. B. Brenner, Nature (London) 339:544-548, 1989; D. H. Raulet, Annu. Rev. Immunol. 7:175-207, 1989) have been characterized recently in Mycobacterium tuberculosis H37Rv as a group of four structurally related nucleotidic or phosphorylated molecules, termed TUBag1 to -4 (tuberculous antigens 1 to 4) (P. Constant, F. Davodeau, M. A. Peyrat, Y. Poquet, G. Puzo, M. Bonneville, and J. J. Fournie, Science 264:267-270, 1994). Here, we analyzed their distribution in different mycobacterial species of the M. tuberculosis group, with special emphasis on the human vaccine Mycobacterium bovis BCG. We show that the same four TUBag1 to -4 molecules are shared by these mycobacteria. Quantitative comparison reveals, however, that while the pathogen M. bovis and M. tuberculosis species produce rather high amounts of TUBag, all of the BCG strains have a surprisingly reduced production of TUBag. These observations suggest that among tuberculous mycobacteria, the bacterial TUBag load could, to some extent, constitute an immunological determinant of mycobacterial virulence for humans.