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Research project

Investigating CD1c lipid-antigen presentation and its role in tuberculosis

Project overview

Tuberculosis (TB) remains a global health pandemic. Notably, TB is the second global killer from an infection after COVID-19, and is becoming increasingly resistant to the antibiotics used to treat it. Unfortunately, despite major research programmes over the last two decades, recent outcomes of novel interventions for TB have been disappointing. Thus, a better understanding of the host-pathogen interaction is urgently required to inform better future therapeutic interventions. We study innate responses to TB mediated by CD1c molecules. Importantly, a growing body of evidence suggests a functional role for CD1c and its restricted T-cells in human TB. However, the molecular mechanisms underpinning CD1c recognition by T-cells, and the functional impact of CD1c immunity in human TB, are not well understood.
To achieve a deeper understanding of CD1c lipid antigen presentation to T-cells and their role in TB, we are pursuing the following aims:
1- Determine the molecular basis underpinning the interaction between the T-cell receptor (TCR) and ligand-loaded CD1c
2- Investigate the structure-activity relationships of host and pathogen-derived lipids on CD1c-restricted T-cells
3- Define the functional consequence of CD1c-restricted T-cell responses to TB infection
This fundamental understanding of the role of CD1c-responsive T-cells in human TB may lead to novel targets for immune intervention to control the global pandemic.

Staff

Lead researcher

Dr Salah Mansour PhD

Associate Professor

Research interests

  • Unconventioanl T cells in health and disease 
  • CD1 group 1 restricted T cell immunity  
  • Structural and molecular mechainsms of CD1 lipid antigen presentation 
Connect with Salah
Other researchers

Dr Ivo Tews

Associate Professor

Research interests

  • Natural products biosynthesis: a complex cascade of catalytic steps in vitamin B6 biosynthesis is characterised by structures or reaction intermediates in the large PLP syntase complexEdit
  • Bacterial biofilms: understanding of RedOx regulated phosphodiesterase activity in dispersal of biofilms to address chronic infections
  • Cancer immunology: together with Cancer Immunology at Southampton we use a structure based apporach in developing novel cancer therapie
Connect with Ivo

Professor Paul Elkington

Director of Inst. for Medical Innovation

Research interests

  • tuberculosis
  • immunopathology
  • diagnosis
Connect with Paul

Collaborating research institutes, centres and groups

Research outputs

Mohamed Ahmed, Jared Mackenzie, Liku Bekele Tezera, Robert Krause, Barry Truebody, Diana Garay Baquero, Andres Vallejo Pulido, Katya Govender, John Adamson, Hayden Fisher, Jonathan W. Essex, Salah Mansour, Paul Elkington, Adrie J. C. Steyn & Alasdair Leslie, 2022, Communications Biology, 5(1317)
Type: article
Liku Bekele Tezera, Magdalena Bielecka, Paul Ogongo, Naomi Walker, Matthew Ellis, Diana J. Garay-Baquero, Kristian Thomas, MICHAELA REICHMANN, David Johnston, Katalin Wilkinson, Mohamed Ahmed, Sanjay Jogai, Suwan N. Jayasinghe, Robert J. Wilkinson, Salah Mansour, Gareth Thomas, Christian Ottensmeier, Alasdair Leslie & Paul Elkington, 2020, eLife, 9
Type: article
Liku Bekele Tezera, Salah Mansour & Paul Elkington, 2019, American Journal of Respiratory and Critical Care Medicine, 201(4)
Type: review