Active Infection & Immunity Genetics & Molecular Biology

Innate-like T cells and integration of host defence

In plain English

AI plain-English summary

A newly discovered class of immune cells—called MAIT cells, a type of innate-like T cell—sits at the crossroads of the body’s fast-acting innate defences and its slower, more precise adaptive immunity, and this project aims to work out exactly how they coordinate that response. The problem is that while scientists know these unconventional T cells exist in human tissues, their precise roles in fighting viruses and shaping vaccine responses remain poorly understood. The researcher’s lab has already shown that these cells are exquisitely sensitive to early infection cues, can help repair damaged barriers, and orchestrate adaptive immunity after experimental vaccination. This project will dig deeper, using new tools to uncover the mechanisms linking MAIT cells to vaccine effectiveness and to severe viral infections like SARS-CoV-2, influenza, and viral hepatitis. If successful, this work could reveal why some people respond better to vaccines than others, and suggest ways to boost immunity against major viral threats. Because the research is fundamental science—exploring how the immune system integrates signals—it may not yield an immediate practical application. But similar fundamental discoveries about T cells have underpinned everything from cancer immunotherapies to modern vaccine design, so a clearer picture of these cells could eventually lead to smarter vaccines or treatments for infectious diseases.

View original technical description
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.

View the original record at the funder ↗

Researchers

Paul Klenerman (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

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