Immunological lung disease // Drug Repurposing

Immunological lung disease

International research team mapping the CD4 and CD8 T cell epitopes of Burkholderia pseudomalleiDr 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.

South Kensington summer picnicKey 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.Catherine Reynolds at an immunology meeting in Keystone, USA 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 propose that selection from responding clones with distinctive TCRs on the basis of functional avidity can direct a preference away from Th1 effector responses, favoring Th2 cytokines.

We have developed several TCR, lung targeted, and inducible (Cre/Lox) and BAC reporter transgenic models to study the impact of TCR structure on T cell function including lung inflammation. We 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.

Next Generation Project Summer lab picnic

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