Mtb is a mucosal pathogen that is transmitted through aerosolized particles that have the ability to interact with the respiratory tract. The mechanisms that contribute to the control of Mtb in the early stages of infection remain unclear. Indeed, not all individuals who are exposed to Mtb get infected with the bacterium. This suggests that humans have evolved innate resistance mechanisms that contribute to the control of Mtb before the induction of an adaptive immune response. To address this, Dr. Gold has been focused on identifying and characterizing innate CD8 T cells. She has shown that humans have innate Mtb-reactive T cells. She has characterized one such subset as MR1-restricted MAIT cells. While in David Lewinsohn's laboratory she determined that a function for MAIT cells is to detect infection with Mtb and other bacteria and fungi. A number of projects are emerging from this discovery and several of these are being conducted in conjunction with Dr. Lewinsohn's laboratory.

As little is known about MAIT cells, we aim to broadly characterize the phenotype, function, and location of pathogen-reactive MAIT cells, those with the capacity to detect intracellular infection. So far our work shows that pathogen-reactive MAIT cells are highly enriched in the human lung, the most common site of infection with Mtb. As a result, studies are ongoing to determine the relationship of MAIT cells with Mtb and the human respiratory tract.

Do MAIT cells have the capacity to discriminate between different pathogens? The combination of a restricted T cell receptor and restriction by a highly conserved HLA-Ib molecule suggests MAIT cells have limited ligand discrimination potential. However, it is unclear if MAIT cells have the ability to discriminate between different pathogens. Work is ongoing to address this question.

We have shown that antigen-inexperienced MAIT cells are programmed in the thymus to respond to infected cells. This intrinsic effector capacity is unique to innate-like T cells. In our lab we are characterizing the requirements that induce the innate effector programming of MAIT cells.

Our studies have also pointed to the existence of other uncharacterized innate-like non-classical CD8 T cells responsive to Mtb-infected cells. Studies are ongoing to define these T cells.