Unconventional T cells and TB
Peptide antigens are typically presented to T cells by highly polymorphic major histocompatibility complex (MHC) Class I and Class II molecules and have been studied extensively in humans and animal models of tuberculosis. However, some T cells can also be activated by non-peptide antigens via MHC-independent antigen presenting systems. The role that these "unconventional" T cells play in the pathogenesis of human tuberculosis is a major focus of the lab.
Resistance to M. tuberculosis
In endemic settings, some adults who are heavily and repeatedly exposed to M. tuberculosis never develop latent tuberculosis infection (LTBI) as defined by a positive tuberculin skin test (TST) or interferon gamma release assay (IGRA). These individuals, may "resist" M.tb infection. We are part of an international consortium that is trying to understand the immune mechanisms underlying this clinical phenotype. Our hope is that we will discover the immune mechanisms that are required for protective immunity to M.tb in humans. This information can then be used to develop new therapies, including vaccines.
- Lu et al. IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure. Nature Medicine 2019
- Simmons JD et al. Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection. Nat Rev Immunol. 2018
- Seshadri C et al Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection. PLoS One. 2017
Advances in flow cytometry and sequencing have transformed immunology by enabling large numbers of parameters to be quantified on single cells in high-throughput. However, the statistical and computational frameworks with which to effectively analyze these large data sets have lagged behind the technological advances. We are collaborating with experts in the emerging discipline of ‘computational immunology’ to develop and apply these tools in our studies.