Structural studies of protein-carbohydrate interactions

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This application proposes to use biophysical techniques of 'x-ray crystallography' and 'surface plasmon resonance' to study the structure and binding of 'germline' and 'matured' antibodies to carbohydrate antigens. The specific recognition of carbohydrates by antibodies is a critical aspect of immune surveillance for microbial pathogenesis and diseased tissue. The antibody response in a new-born organism is composed largely from antibodies constructed from inherited, or 'germline,' gene segments that are subject to natural selection based on pathogen prevalence. This is a critical consideration for antibodies specific for carbohydrate antigens as they generally do not stimulate an immune mechanism called 'affinity maturation' that generates highly-specific and tightly-binding antibodies. The resulting germline antibodies have relatively low affinity to carbohydrate antigens, which has limited the study of the three-dimensional mechanisms of specificity of anti-carbohydrate antibodies and there exist just a few reports of the structures of antibody fragments in complex with carbohydrate antigen.