Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens
Rlv. Skjot et al., Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens, INFEC IMMUN, 68(1), 2000, pp. 214-220
Culture filtrate from Mycobacterium tuberculosis contains protective antige
ns of relevance for the generation of a new antituberculosis vaccine. We ha
ve identified two previously uncharacterized M. tuberculosis proteins (TB7.
3 and TB10.4) from the highly active low-mass fraction of culture filtrate.
The molecules were characterized, mapped in a two-dimensional electrophore
sis reference map of short-term culture filtrate, and compared with another
recently identified low-mass protein, CFP10 (F. X. Berthet, P, B. Rasmusse
n, I. Rosenkrands, P. Andersen, and B. Gicquel. Microbiology 144:3195-3203,
1998), and the well-described ESAT-6 antigen. Genetic analyses demonstrate
d that TB10.4 as well as CFP10 belongs to the ESAT-6 family of low-mass pro
teins, whereas TB7.3 is a low-molecular-mass protein outside this family. T
he proteins were expressed in Escherichia coli, and their immunogenicity wa
s tested in cultures of peripheral blood mononuclear cells from human tuber
culosis (TB) patients, Mycobacterium bovis BCG-vaccinated donors, and nonva
ccinated donors. The two ESAT-6 family members, TB10.4 and CFP10, were very
strongly recognized and induced gamma interferon release at the same level
(CFP10) as or at an even higher level (TB10.4) than ESAT-6, The non-ESAT-6
family member, TB7.3, for comparison, was recognized at a much lower level
, CFP10 tvas found to distinguish TB patients from BCG-vaccinated donors an
d is, together with ESAT-6 an interesting candidate for the diagnosis of TB
. The striking immunodominance of antigens within the ESAT-6 family is disc
ussed, and hypotheses are presented to explain this targeting of the immune
response during TD infection.