Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have discovered how evolution may have lumbered humans with allergy problems. The team from the Randall Division of Cell & Molecular Biophysics, King's College London are working on a molecule vital to a chicken's immune system which represents the evolutionary ancestor of the human antibodies that cause allergic reactions. Crucially, they have discovered that the chicken molecule behaves quite differently from its human counterpart, which throws light on the origin and cause of allergic reactions in humans and gives hope for new strategies for treatment. The work is published today (13 June) in The Journal of Biological Chemistry.
Researcher, Dr Alex Taylor said: "This molecule is like a living fossil – finding out that it has an ancient past is like turning up a coelacanth in your garden pond. By studying this molecule, we can track the evolution of allergic reactions back to at least 160 million years ago and by looking at the differences between the ancient and the modern antibodies we can begin to understand how to design better drugs to stop allergic reactions in their tracks."
The chicken molecule, an antibody called IgY, looks remarkably similar to the human antibody IgE. IgE is known to be involved in allergic reactions and humans also have a counterpart antibody called IgG that helps to destroy invading viruses and bacteria. Scientists know that both IgE and IgG were present in mammals around 160 million years ago because the corresponding genes are found in the recently published platypus genome. However, in chickens there is no equivalent to IgG and so IgY performs both functions.
Lead researcher, Dr. Rosy Calvert said: "Although these antibodies all started from a common ancestor, for some reason humans have ended up with two rather specialised antibodies, whereas chickens only have one that has a much more general function.
"We know that part of the problem with IgE in humans is that it binds extremely tightly to white blood cells causing an over-reaction of the immune system and so we wanted to find out whether IgY does the same thing."
By examining how tightly IgY binds to white blood cells the researchers have found that it behaves in a much more similar way to the human IgG, which is not involved in allergic reactions and binds much less tightly.
Professor Brian Sutton, head of the laboratory where the work was done said: "It might be that there was a nasty bug or parasite around at the time that meant that humans needed a really dramatic immune response and so there was pressure to evolve a tight binding antibody like IgE. The problem is that now we've ended up with an antibody that can tend to be a little over enthusiastic and causes us problems with apparently innocuous substances like pollen and peanuts, which can cause life-threatening allergic conditions."
The next stage of the work is to examine in very fine detail the interaction between the antibodies and the surface of the white blood cell. This is with a view to designing drugs that could alter this interaction and therefore 'loosen' the binding of IgE, making it more like its chicken counterpart.
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Notes to Editors
This research is published in The Journal of Biological Chemistry: Taylor et al., 'Avian IgY binds to a monocyte receptor with IgG-like kinetics despite an IgE-like structure', The Journal of Biological Chemistry, 283: 16384-16390
This research is funded by a £300K grant from the UK's Biotechnology and Biological Sciences Research Council (BBSRC).
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £380 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. http://www.bbsrc.ac.uk
About King's College London
King's College London is one of the top 25 universities in the world (Times Higher 2007) and the fourth oldest in England. A research-led university based in the heart of London, King's has 19,300 students from more than 130 countries, and 5,000 employees. King's has an outstanding reputation for providing world-class teaching and cutting-edge research. The College is in the top group of UK universities for research earnings and has an annual income of approximately £400 million. An investment of £500 million has been made in the redevelopment of its estate.
King's has a particularly distinguished reputation in the humanities, law, social sciences, the health sciences, natural sciences and engineering, and has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA. It is the largest centre for the education of healthcare professionals in Europe and is home to five Medical Research Council Centres – more than any other university.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are working together to create the UK's largest Academic Health Science Centre (AHSC). The AHSC will bring together the widest range of clinical and research expertise in the UK – strengths that will be used to drive improvements in care for patients, allowing them to benefit from breakthroughs in medical science and receive leading edge treatment at the earliest possible opportunity.
For further information visit: http://www.londonsahsc.org
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