Lung Immunology

Dr Rosemary Boyton, Head of Group

Molecular Immunology of Lung Disease

Dr Rosemary Boyton established the Lung Immunology Group having been awarded an MRC Clinician Scientist Fellowship. The mission of the Lung Immunology Group is to gain an understanding of the molecular interactions of T lymphocyte responses leading to respiratory disease, major goals being to elucidate pathological mechanisms and design effective and specific therapies including vaccine development.

Key research areas:

• The impact of T cell receptor (TCR) structure on T cell effector function
• The role of innate and adaptive immunity in the development and regulation of allergic and infectious lung inflammation
• Human TCR/HLA transgenic models for analysis of disease pathogenesis, for example, allergic asthma
• Targeted and inducible (Cre/Lox) transgenic models to study innate and adaptive immune mediated lung inflammation
• Class II epitope mapping using HLA transgenics and tetramer technology
• Vaccine development for infectious, non-infectious and allergic disease

We have shown that CD4 T cells selected by antigen under Th2 polarizing conditions favour elongated TCRalpha chain complementarity determining region (CDR3) predicted on structural grounds to bind peptide/MHC with a lower affinity to their Th1 counterparts. This data led to the “structural hypothesis” that under Th2 favoring conditions, cells are selected by low affinity for peptide/MHC and this is achieved by selecting TCR chains with sterically obstructive CDR3alpha loops.

We have developed several TCR, lung targeted, and inducible (Cre/Lox) transgenic models to study the impact of TCR structure on T cell function including lung inflammation. We now use these models to study innate and adaptive immune mechanisms in the development and regulation of pulmonary inflammation, airway hyperreactivity and airway remodeling in infectious and allergic inflammation.

We are interested in the processes underlying progressive lung damage in bronchiectasis, our hypothesis being that it results from aberrant regulation of the innate and/or adaptive immune response in the context of chronic bacterial infection.

Funding for the group comes from the Medical Research Council, Asthma UK, BBSRC, NIH, Welton Foundation, NHLI Foundation, and Royal Brompton NHLI Clinical Research Committee.

The  Lung Immunology Group is part of the MRC & Asthma UK centre in Allergic Mechanisms of Asthma and the Centre for Respiratory Infection funded by the Wellcome Trust. 

The Group has close links with clinicians and scientists at Imperial College Healthcare NHS Trust. Biomedical Research Centre and Royal Brompton & Harefield NHS Foundation Trust Biomedical Research Unit facilitating patient based translational studies.

Through an NIH-funded research programme, we are mapping the CD4 and CD8 T cell epitopes of Burkholderia pseudomallei as part of the international consortium, the Immune Epitope Database (www.IEDB.org).  It is a large scale, high-throughput, patient and HLA transgenic model based analysis of T cell epitopes in the immune response to Burkholderia pseudomallei, the causative agent in melioidosis. The candidate panel of epitopes are being analysed in the context of protection and pathogenicity. Burkholderia pseudomallei (previously called Pseudomonas pseudomallei ) is the causative agent of melioidosis, a serious disease of man and animals that occurs primarily in S.E. Asia, N. Australia and other tropical areas. B. pseudomallei is an environmental Gram-negative saprophyte present in wet soil and rice paddies in endemic areas. The highest documented infection rate is in northeastern Thailand, where melioidosis accounts for 20% of all community-acquired septicaemias. Disease occurs after bacterial contamination of breaks in the skin or by inhalation after contact with water or soil. There is no licensed vaccine against meliodosis, and the bacterium is resistant to many antibiotics.

Imperial College London Dr Rosemary Boyton & Professor Daniel Altmann (Project Leads), Dr Louise Kim (project manager), Dr Karen Chu (post-doctoral scientist), & Dr Bernadette Byrne (Protein Facility) Khon Kaen Unviersity Faculty of Associated Medical Sciences, Thailand Professor Ganjana Lertmemongkolchai & Darawan Rinchai. University of Newcastle Professor John H. Robinson & Dr Julie Musson (post-doctoral scientist). London School of Hygiene and Tropical Medicine London Dr Greg J Bancroft & Dr Natasha Patel (post-doctoral scientist). Department of Molecular Engineering of Proteins, CEA-Saclay, Gif sur Yvette, France Prof Bernard Maillere.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Postdoctoral research associates from the lab are involved in the the Next Generation Project (NGP) at Imperial. This project aims to use the wealth of scientific knowledge and enthusiasm within the postdoctoral research community at Imperial to ignite an interest in science from primary school children.