PROJECT SUMMARY Wuhan, China is the epicenter of a rapidly spreading pandemic the World Health Organization (WHO) has officially designated as COVID-19. COVID-19 is caused by SARS-CoV-2, but how it is spread from person to person is still unclear. The asymptomatic presentation of the disease, and widespread travel out of Wuhan have permitted its rapid dissemination. As of March 16, 2020, there are over 175,000 cases affecting 162 countries with over 6,700 fatalities worldwide. SARS-CoV-2 is positive-sense RNA virus infecting vertebrate hosts that exists in a group of closely related co-evolving entities of which two others – SARS-CoV and MERS-CoV – have caused recent epidemics. Due to the complexity of anti-viral immunity, experience with other viruses has shown that swift success in vaccine development is by no means assured. A major challenge is the difficulty in adequately characterizing T cell-mediated recognition of viral epitopes. Finding the major shared specificities in COVID-19 subjects will help us understand what the most important CD4+ and CD8+ T cell responses will be. These findings can be deployed to determine the optimal vaccine formulation so as to elicit these T cell specificities. We hypothesize that T cell responses to specific epitopes of SARS-CoV-2 will be critical for its control in infected patients across diverse HLA haplotypes, and that a comprehensive mapping of epitopes recognized by those who clear the virus and their cognate TCRs will facilitate the development of the most effective vaccines for COVID-19 treatment. To pursue this hypothesis, we will employ some very new tools for T cell responses that have recently been developed at Stanford and the Princess Margaret Cancer Center, together with COVID-19 survivors’ blood samples obtained in Toronto, Hong Kong and Stanford.