Innate-like T cells and integration of host defence (360G-Wellcome-222426_Z_21_Z)

This research project aims to define the key roles of newly defined T cell subsets, and how they integrate signals between innate and adaptive immune responses to optimise host defence. Recent work on immune responses in human tissues has revealed the complex landscape of immunity and emphasised the role of poorly-defined unconventional T cell subsets. In the past 5 years my lab has defined some of these roles including 3 main findings - a striking sensitivity to innate cues, relevant for initiation of protective responses to viruses, a wide palette of functions including a role for barrier repair, and the ability to co-ordinate adaptive responses following experimental vaccination. In this application I aim to take these findings much further, harnessing a set of novel tools and aiming: 1) To define the mechanisms underpinning the link between MAIT cells (as a paradigm for innate-like T cells) and vaccine responsiveness; 2) To understand the mechanisms by which such cells may impact on outcomes of severe viral infection. Overall this work is highly relevant to major health challenges such as SARS-CoV-2, influenza, viral hepatitis and microbial infection - and to the vaccines needed to combat these challenges.