Investigating CD1c lipid-antigen presentation and its role in tuberculosis

Tuberculosis (TB) remains a global health pandemic. Notably, TB is the second global killer from an infection after COVID-19, and is becoming increasingly resistant to the antibiotics used to treat it. Unfortunately, despite major research programmes over the last two decades, recent outcomes of novel interventions for TB have been disappointing. Thus, a better understanding of the host-pathogen interaction is urgently required to inform better future therapeutic interventions. We study innate responses to TB mediated by CD1c molecules. Importantly, a growing body of evidence suggests a functional role for CD1c and its restricted T-cells in human TB. However, the molecular mechanisms underpinning CD1c recognition by T-cells, and the functional impact of CD1c immunity in human TB, are not well understood.
To achieve a deeper understanding of CD1c lipid antigen presentation to T-cells and their role in TB, we are pursuing the following aims:
1- Determine the molecular basis underpinning the interaction between the T-cell receptor (TCR) and ligand-loaded CD1c
2- Investigate the structure-activity relationships of host and pathogen-derived lipids on CD1c-restricted T-cells
3- Define the functional consequence of CD1c-restricted T-cell responses to TB infection
This fundamental understanding of the role of CD1c-responsive T-cells in human TB may lead to novel targets for immune intervention to control the global pandemic.