Chetan Seshadri

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This week we profile a recent publication in The Journal of Immunology from
the lab of Dr. Chetan Seshadri (pictured) at the UW Department of Medicine.

Can you provide a brief overview of your lab’s current research focus?

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.

What is the significance of the findings in this publication?

Our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines, such as BCG, and show that lipid Ag-specific T cells are resident in the lungs, where they may contribute to protective immunity.

What are the next steps for this research?

The next steps are to see if these cells actually do have a mechanistic role in the remarkable protective efficacy that is provided by intravenous BCG, as published by our collaborators last year (Darrah et al. Nature 2020). If so, it would argue that the field of TB vaccine development has to think beyond subunit protein vaccines and consider lipid Ags as well.

This work was funded by:

NIH and BMGF.

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