Paul Klenerman
Contact information
paul.klenerman@medawar.ox.ac.uk
Kate Southey
kathryn.southey@ndm.ox.ac.uk
Peter Medawar Building
Colleges
Paul Klenerman
Sidney Truelove Professor of Gastroenterology
Infectious diseases such as HIV, hepatitis B and C, affect hundreds of millions of people worldwide. Our group works on the immune response to these infections, focusing on both the host and the pathogen. As there is currently no vaccine to prevent hepatitis C infection, many of our projects have addressed aspects of chronic hepatitis C virus (HCV) infection and vaccine responses. In addition, our group also looks at a range of viruses and bacteria. Overall our main contributions to date have been to define mechanisms of viral persistence, including: T cell escape, antagonism, original antigen sin, integration of non-retroviral RNA viruses; to define the key features of successful immune responses against HCV, leading to trials of a T cell vaccine; and to define the distinctive CD161+ T cell population, which dominates in the human liver.
We are currently working on three main strands of research:
1. CD161++/MAIT cell biology. These lymphocytes, which are abundant in human blood and highly enriched in the liver, have the capacity to respond to both bacterial and inflammatory signals. We are trying to understand their in vivo role in host defence and immunopathology, through the analysis of patients and in vitro studies of function and activation.
2. HCV immune defence. In collaboration with the groups of Ellie Barnes and Adrian Hill, we are involved in vaccine studies using adenoviral vectors to track vaccine-induced cells and analyse their capacity to recognise viral variants. Upcoming studies include an analysis of host responses in relation to novel drug therapies and the use of new viral sequencing approaches to define the impact of host immunity.
3. Memory inflation. Some persistent virus infections induce a striking host response, which we have termed memory "inflation"; this includes the generation of very large functional T cell populations, which can increase with time. While this was first noted in cytomegalovirus infections, we have found a similar profile of cells after adenoviral vector vaccination. Our group is working to define the qualities of these induced cells, and the critical factors that drive memory inflation.
Recent publications
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Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020
Working paper
Thompson CP. et al, (2020), Eurosurveillance, 25
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Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis
Journal article
Slevin SM. et al, (2020), Journal of Crohn's and Colitis, 14, 1446 - 1461
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Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis.
Journal article
Sasson SC. et al, (2020), Clinical and experimental immunology
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MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans.
Journal article
Esposito I. et al, (2020), Science translational medicine, 12
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MAIT Cells in Health and Disease.
Journal article
Provine NM. and Klenerman P., (2020), Annual review of immunology, 38, 203 - 228