CD1b as a vaccine target for tuberculosis: A hidden GEM?

Tuberculosis is currently the most deadly infectious disease worldwide, killing an estimated 1.7 million people in 2016. The only licensed vaccine currently available is BCG, which is only 70% effective. While most vaccines work by inducing antibodies, mycobacterium tuberculosis (or Mtb for short) hides inside cells, preventing antibodies from reaching it. T cells, which help kill intracellular pathogens, seem to be much more important for protection against tuberculosis. Conventional T cells have hugely diverse receptors which bind pathogen peptides presented on MHC molecules, causing the T cells to differentiate and divide.

Unlike most bacteria, Mtb has a waxy coat containing lipids known as mycolates. Mycolates are presented by CD1 rather than MHC molecules, binding to conserved receptors on germline-encoded mycolyl lipid reactive (GEM) T cells, an unconventional T cell subset discovered only four years ago. In a recent study by the universities of Southampton and Bangor, researchers found that CD1b was present in the lungs of tuberculosis patients, suggesting these cells could play a role in the immune response to Mtb. As different Mtb strains produce mycolates with slightly different structures, understanding how these lipids bind receptors will be necessary to develop novel anti-TB vaccines targeting GEM T cells. By adding different mycolates to cells expressing GEM T cell receptors, the researchers found that the “head” of the lipid wasn’t important for specificity, while the “tail” was, affecting how strongly T cells were activated. Thus by manipulating the chemical structure of the mycolate tail, future vaccines could be optimised to maximise the GEM T cell response, hopefully improving efficacy.