The immune system in vaccination and allergy
Immune activation in health and disease. The immune system provides a protective response against pathogens, but may also be activated inappropriately leading to allergy and other unwanted immune conditions. The Sattentau lab works on harnessing the beneficial sides of immune activation by developing vaccine antigens and adjuvants against major human viral pathogens, with particular emphasis on the human immunodeficiency virus type-1, HIV-1. Antigen design work involves protein engineering strategies coupled with post-translational modification and antigenicity and immunogenicity analyses. Adjuvant studies focus on analysis of immune activating mechanisms using in vitro and in vivo immunological systems. Our vaccine-oriented work is supported by European Union and Bill and Melinda Gates Foundation grants with the ultimate goal of translating outcomes into clinical trials for vaccine efficacy in man. Our work on unwanted immune activation is focussed on how T helper type-2 (Th2) allergic immune responses are triggered by post-translationally modified antigens, with emphasis on the role of oxidative stress. Oxidative stress which may occur naturally in the environment or be created as a result of industrial processing such as food processing, leads to the adduction of reactive chemical species to proteins. We are focussing on the study of one particular species of oxidative adduct called a reactive carbonyl, which triggers T cell activation by a novel pathway of MHC class-II-peptide stabilisation. Current work is focussed on understanding the mechanism of Th2 activation and developing model systems to interrogate the role of reactive carbonyls in allergy and other immune disorders, with emphasis on peanut allergy and asthma.