Early works on MPB70 and MPB83 (Mycobacterium bovis) or MPT70 and MPT83 (Mycobacterium tuberculosis)The first observations on MPB70 were likely made already in 1960 by Lind [1,2]. MPB70 was originally identified as a protein highly expressed by M. bovis Bacille CalmetteGuérin (BCG) substrain Tokyo by Nagai [3]. MPB70 has a relative mobility of 0.70 by native polyacrylamide gel electrophoresis at pH 9.4, and the term 'MPB' refers to a protein from M. bovis, hence its name while 'MPT' refers to proteins from M. tuberculosis. The protein was purified from BCG culture filtrate using conventional purification methods and was found to induce delayed type hypersensitivity in guinea pigs immunized with some BCG strains, but not by certain other BCG strains [4,5]. Antibody responses followed a similar pattern [5]. Two-dimensional electrophoresis showed the presence of MPB70 in the strains that induced delayed type hypersensitivity [4]. This was soon confirmed using rabbit antibodies raised against MPB70. These antibodies reacted with MPB70 and formed a distinct precipitation line in crossed immunoelectrophoresis [6]. By radioimmunoassay inhibition tests, it was possible to quantify MPB70 [6], and MPB70 was clearly demonstrated, but in very low amounts in the strains that were negative in the previous investigations [6]. The observations formed the basis for dividing BCG strains into two main groups, those that express high levels of MPB70 and those that express minor amounts of MPB70. Those that express high levels of MPB70 are BCG Tokyo, Moreau, Russia, Sweden, Birkhaug (Bergen), Romania (Cantacuzinho strain), and those that express low levels are BCG Pasteur, Danish 1331, Glaxo, Tice and Beijing. This subdivison of BCG strains has been correlated to how BCG was distributed from the Pasteur institute during the 1920s. The comparatively low levels of MPB70 in sonicated extracts of whole washed bacterial cells strongly indicated that MPB70 was actively secreted Abstract MPB70 and MPB83 are among the most studied mycobacterial antigens. They are highly homologous proteins within Mycobacterium tuberculosis complex members, and the orthologs in different members of the complex are virtually identical. They are major antigens highly expressed by Mycobacterium bovis and considerably less abundantly expressed by M. tuberculosis. There are two genes encoding these proteins within an operon of six genes. MPB70 and MPB83 are encoded as precursor proteins with typical signal peptides for export through the general secretory pathway. MPB70 is a soluble secreted protein cleaved by signal peptidase I, while MPB83 is a glycosylated lipoprotein processed by signal peptidase II and located at the surface, possibly with the lipid tail coupled to the N-terminal cystein embedded in the mycobacterial outer membrane. The expression of these genes is controlled by the transcriptional regulator SigK, and a point mutation in SigK explains why some Bacille Calmette-Guérin (BCG) strains express only minute amounts of MPB70 and MPB83. BCG strains t...