Understanding and manipulating Antibody Dependent Cell Cytotoxicity (ADCC) by human Natural Killer (NK) cells

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Biologists have given names to nearly all the different protein molecules that mediate communication between human cells. Now, the audacious goal of contemporary cell biology is to understand how the billion proteins in a live cell allow them to move, multiply, contribute to a brain or defend us against viruses and bacteria. Imaging where and when proteins interact with each other has a major role to play at this frontier. Recent imaging of just a few types of proteins has already led to important new concepts in how immune cells communicate with each other and how they recognize signs of disease. High-resolution microscope images of immune cells contacting other cells have revealed temporary membrane structures, often called immune synapses, similar to the synapses that nerve cells make with one another for communication. Proteins commonly segregate into specific regions at the contacts between cells, and exploring how such changing arrangements of proteins occur and how they control immune cell communication is the new science opened up by the immune synapse concept. Over the last decade the use of antibodies has revolutionised the treatment of severe human diseases, such as non hodgkins lymphoma (NHL) and rheumatoid arthritis (RA). One way that these antibodies work is by triggering Natural Killer cells to directly kill diseased target cells. Crucially, nobody has yet determined what happens at immune synapses when antibodies trigger killing of diseased cells. Here, we plan to use state-of-the-art technologies to image immune synapses during antibody-medaited killing with a view to learning how to best optimise antibodies for this function. We will apply the understanding gained from these basic studies to the rational design of modified antibodies for optimal efficiency in a range of disease treatments.