Govinda Sharma

BC Cancer Agency · Canada's Michael Smith Genome Sciences Centre

Though it is understood that T-cells are a critical component of the immune system’s ability to destroy foreign invaders (such as pathogenic bacteria, viruses, fungi, and parasites) as well as identify and attack cancerous cells, very little is known regarding the specific molecular determinants (antigens) that T-cells recognize in order to carry out these functions. There is a severe lack of linked T-cell receptor/antigen pairs - fewer than 700 verified pairs are described in the literature while hundreds of millions of T-cell receptor sequences have been documented and a nearly limitless number of possible T-cell antigens could exist. I have developed a novel method for high-throughput T-cell antigen discovery that matches the sensitivity of conventional, gold-standard approaches but with the added advantage of being able to query more than a million distinct peptide coding sequences (>100x more than is feasible with conventional methods) for their ability to elicit reactivity from a given TCR. My current work is focused on continuing to benchmark the approach in a variety of model T-cell/antigen systems to open the door for the scientific community to generate linked TCR/antigen data at a scale large enough to allow researchers to better understand basic T-cell biology, develop better predictive models of T-cell reactivity, and rationally design T-cell based immunotherapeutics for the treatment of cancer, infectious diseases, transplant rejection, and autoimmune disorders.