Investigating gamma delta T cells
An interview with Dr. Payal Damani-Yokota
Dr. Payal Damani-Yokota from the University of Massachusetts, Amherst, talks about her work to help uncover the signals that drive development and function of gamma delta T cells.
The scope of her research and the questions she is asking
For the last 6 years, I have been working toward my PhD at the University of Massachusetts in Amherst under the tutelage of Dr. Cynthia L. Baldwin. The overarching goal of our research is to uncover the signals that drive development and function of gamma delta (γδ) T cells. What makes these cells especially interesting is that they express a family of scavenger receptor cysteine-rich (SRCR) glycoproteins called Workshop Cluster 1 (or WC1) that functions as a hybrid pattern recognition receptor/coreceptor exclusively in conjunction to the γδ TCR. Our research previously showed that WC1-expressing γδ T cells are indispensable for response to bacterial antigens such as Leptospira; and upon engagement with ligand, the endodomains can signal via phosphorylation of conserved serines and tyrosines. We have also found that in response to Leptospira, one subset of WC1+ cells produces IFNγ, while the other does not. While we knew a lot about WC1 function and its importance in recall responses, we did not know how many WC1 molecules a single γδ TCR+ cell could express, or how many of these molecules were required to direct immune responses by γδ T cells. It was also not known when and where these molecules are first detected during T cell development, or how these functional subsets of γδ T cells were transcriptionally programmed.
To answer these questions, I flow-sorted purified populations of WC1+ γδ T cell subsets and developed a culture system such that I could expand 78 different WC1+ γδ T cell clones from a single cell origin where primary γδ T cells could proliferate in vitro for up to 10 weeks. Using [Applied Biosystems] TaqMan Assays, I evaluated WC1 gene transcription on each clone to evaluate the WC1 gene expression. The co-transcription of WC1 genes showed that WC1s can be expressed by themselves or in combinations with some overlap between the two subsets. Despite this overlap, the Leptospira-responsive WC1+ memory γδ T cell clones showed significantly higher propensity to express WC1 molecules that are known to bind to the pathogen. I also found that WC1 molecules are exclusively expressed on thymic γδ T cells and stratify into the mostly nonoverlapping subsets early in development. This is particularly important because unlike conventional αβ T cells, γδ T cells bifurcate into functional subsets during thymic development guided by distinct transcriptional programming.
The next steps
My insatiable curiosity about where and how γδ T cells develop and why and how they function has led me to investigate even more. The beauty of innate-like lymphocytes is that they have the clonotypic TCRs as well as accessory receptors that help them to respond early and fast, and to expand despite being tiny populations in blood. γδ T cells act as bridges between the innate and adaptive immunity, thereby making for an elegant, synchronous, pathogen-combating immune system. On a global note, my research has led me to ask if and where such lateral systems can exist in humans and mice, where PRR/co-receptor molecules partake in recognition of complex antigens and can help in producing functional responses to protect against “damaged/stressed self” as well as “non-self.” So, I am packing up the lessons learned from my PhD and taking them “to go,” as I embark on a venture toward cancer immunology in my next gig as a postdoc.
Payal Damani-Yokota, PhD
University of Massachusetts, Amherst
Cellular and Molecular Immunology
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