Vδ1 γδ T cells
We are interested in understanding what signals regulate the activity of human Vδ1 γδ T cells. Most of these cells are found in peripheral tissues and appear to be tissue-resident. We have been studying the interaction of a subset of these cells with the lipid-presenting MHC-like proteins CD1c and CD1d. We are using structural, biophysical and functional approaches to understanding what these cells respond to in the tissue, in the context of healthy (homeostasis) and diseased tissue. We are currently investigating these cells in lung, colon and neuronal tissue using single-cell transcriptomic profiling to understand effector profiles, TCR repertoire and antigen specificity.
Vγ9Vδ2 γδ T cells
This population of human γδ T cells predominates in the blood where they comprise 2-10% of circulating T cells in a healthy human donor. They can expand to become the majority of T cells in certain microbial infections and cancers, activated through the presence of small, pyrophosphate containing metabolites collectively (and inappropriately) called phosphoantigens or pAgs. It is clear the Vγ9Vδ2 TCR does not directly contact these pAgs and instead are regulated through the direct interaction of these pAgs with a set of butyrophilins (BTNs) molecules on the target cell. We seek to understand the molecular signals that regulate the activity of these T cells through the butryophilins and identify any additional factors that may contribute to Vγ9Vδ2 activation and regulation.
MR1 restricted T cells
MR1 belongs to the MHC superfamily of proteins. It presents small metabolites to a population of T cells expressing an αβ T cell receptor. We call this T cell population MR1 restricted T cells or MR1Ts. A subset of this population is call Mucosal Associated Invariant T (MAIT) cells. We seek to understand the full repertoire of T cells that respond to MR1 and, conversely, the repertoire of ligands that MR1 can bind, and present, to these T cells in the context of infection and disease.
Located in the MHC region alongside the highly polymorphic HLAs (HLA-A, -B and -C) are the nonclassical MHCs, HLA-E, -F and -G. These proteins have more specialized tissue expression and are much less polymorphic than their classical counterparts. We are particularly interested in HLA-F and the particular functional states in which it can engage with effector cells. We are studying this protein in the context of cancer, viral infections and reproduction
Several projects in the lab are focused on understanding how the immune systems of species divergent from human have adapted to their environments. We are investigating immune receptors and antigen presenting molecules in species such as frog and shark.
Regulatory T cells
Regulatory T cells or “Tregs” play a critical role in modulating inflammation. They also can be co-opted by cancer cells to suppress anti-tumor immunity. Despite their important role in host homeostasis and disease, little is known about the antigen-recognition determinants of their activity. We are interested in thymic-derived Tregs and study the molecular determinants that regulate their development and activity in the tissue.