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Understanding the mechanisms by which immune receptors guide T and B-cells to eliminate pathogens is critical to understanding how cancer cells are detected and targeted for destruction, and how autoimmune disease can be propagated and organ transplants rejected. It is crucial for rational design of vaccines and receptor-based immunotherapies including monoclonal antibody and cell therapies and is central to our understanding of whether provoking specific immune responses will be a help or a hinderance in various disease settings.