A new way of identifying antigens on the bacteria that causes
tuberculosis (TB) may help in the search for a vaccine for this
deadly disease.
Antigens are proteins on the cell surface of the bacteria that
cause TB (Mycobacterium tuberculosis) that evoke an immune
response in infected people. These TB antigens are incompletely
understood, which is an obstacle in finding a vaccine against the
disease.
Previous research has shown that, when there is limited oxygen
available, M. Tuberculosis changes its metabolic state in
the host's body - and can reactivate later when oxygen becomes
available. In this state M. Tuberculosis doesn't
seem to replicate - this is known as latency and might explain the
high levels of the population who are infected with TB but have no
symptoms.
The researchers, led by Robert Wilkinson of the MRC's National
Institute for Medical Research (NIMR; now part of the Francis
Crick Institute) and the University of Cape Town, therefore
decided to look into antigens on M. Tuberculosis that are
related to this oxygen status.
In the lab, the scientists subjected M. Tuberculosiscell cultures to a prolonged lack of oxygen and identified a set of
genes that appeared to play a role in enabling the cells to survive
- called 'enduring hypoxic response' (EHR) genes. The EHR genes
produced a response from T cells - immune cells that fight
infections such as TB and are activated in the presence of
antigens.
Out of the EHR genes, the team identified some as possible
antigens. They did this by analysing a combination of data from theM. Tuberculosis genomesand information about immune cell
responses from their experiments.
Professor Wilkinson explained: "This is the first evaluation of
the ability of EHR genes to induce a human T cell response. We have
identified novel immunodominant molecules - those which produce the
strongest immune response. These could be characterised further to
better understand the mechanism and importance of low oxygen
conditions when TB infects people in real life (in vivo).
"Overall, our findings support the hypothesis that it
is possible to predict antigens using genomic data."
He added that his team's approach may also help in
the search for antigens on pathogens that cause other diseases.
Professor Wilkinson worked with colleagues in NIMR's
Division of Mycobacterial Research and collaborators from Imperial
College London, Cape Town and Seattle. The paper, Bioinformatic and empirical analysis of novel
hypoxia-inducible targets of the human antituberculosis T cell
response, was a featured article in the Journal of
Immunology.