An interview with Dr Paul Klenerman
January 2020
Dr Paul Klenerman is an honorary consultant in microbiology at the University of Oxford, and a member of the Microbiology Society. In this interview he tells us more about his research on mucosal-associated invariant T cells and how this could impact disease eradication.
Tell us more about your research.
I work on the interaction between the immune response and microbes. The work started out looking at how T cells control, or fail to control, chronic viral infections such as HIV and hepatitis C virus (HCV). Our work showed some aspects of the differences between successful and unsuccessful immune responses, and this has been harnessed in the development of vaccines for HCV using novel adenoviruses.
We have become really interested in how these adenoviruses work to induce such strong immune responses. They seem to have a capacity to persist in long-lived cells and boost the T-cell reactivity over time. So the work is uncovering some basic aspects of immunity and virology – and also hopefully helping turn such viruses into a new generation of vectored vaccines.
Meanwhile, drug development in the area of hepatitis C has progressed enormously and now patients can be readily cured with tablet treatments – with a big issue remaining of how we best identify those infected.
You have worked on liver immunity and mucosal-associated invariant T cells. Can you tell us more about the importance of these cells?
The work on liver immunity has brought the lab into the area of unconventional T cells, and we have discovered that the liver is highly enriched in a previously overlooked set of lymphocytes called mucosal-associated invariant T cells (MAIT cells).
These cells are a very distinctive blend of innate and adaptive immune cells which possess a range of interesting antimicrobial functions. Such cells can recognise a ligand (5-OPRU) derived from metabolic intermediates of microbial riboflavin synthetic pathways – thus they can sense the presence of invasive microbes as well as commensals in the microbiome.
They are able to distinguish between the two, according to the level of accompanying signals from tissue damage and inflammatory responses (cytokines and interferons), to which they are very sensitive.
We discovered that they can use such inflammatory cues to respond to viruses as well – including hepatitis C virus and influenza challenges – even in the absence of bacterial ligands. MAIT cells turn out to therefore have roles in host-defence against bacteria and yeast; in protection against lethal virus infection; and more recently, also in the repair of mucosal barriers.
Why is this research important to microbiology?
In future, we want to understand more about how microbes in the gut cross-talk with MAIT cells and related T-cell populations. Such cells are positioned perfectly in the epithelium to receive signals from the microbiome and interpret them for the immune system. This can potentially influence the response to vaccines – an area we are actively researching as it has a far-reaching impact. But, we will also investigate the potential impacts on inflammatory diseases and cancer, as well as protection against infectious diseases.
