The Section works on the interaction of (complex) carbohydrate determinants with monoclonal antibodies (MAbs). The elucidation of this interaction - in great molecular detail - is important since it pertains to all ligand- protein interactions. Thus, drug-receptor, effector-receptor as well as viral-receptor interactions may be clarified. We are executing: 1) Physico-chemical studies on antibody/antigen systems; 2) The synthesis of ligands for affinity studies; 3) The manipulation of immunoglobulin genes to produce specifically mutated genes expressing altered antibodies, and 4) The study of immunodeterminants of bacteria causing significant diseases on a global scale, so as to evaluate procedures for vaccine development. We have determined the specific interaction between microbial polysaccharides such as dextran and a number of monoclonal antibodies in the past. Continuing this work, we have measured the enthalpy and entropy of interaction for a number of anti-dextran and anti-galactan monoclonal antibodies. We have prepared many complex fragments of the capsular polysaccharide of Shigella dysenteriae type 1 by sophisticated syntheses, and have mapped the binding area of a monoclonal antibody towards this disease-causing micro- organism. In this manner, the immunodeterminant of this polysaccharide could be defined. We have studied the way in which immunoglobulins recognize specific determinants amidst nonspecific flanking sequences.
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