Studies of these Fab-peptide complexes should benefit the understanding of antigen recognition by their cognate antibodies in general. The solution structure and dynamics of a fifteen peptide (derived from HIV-1 gp120 protein) when bound to several cognate Fabs (antigen binding fragment of an antibody) will be determined using solution NMR techniques. This peptide was used to raise a series of monoclonal antibodies, all of which neutralize the HIV-1 virus and inhibit T4 cell fusion, although to quite different extents. Two of these antibodies, 5023 and 5025A, will be complexed with this peptide and the structural and dynamic properties of the peptide when it is bound to each Fab will be examined using multi-dimensional solution NMR methods. Studies of these Fab-peptide complexes will entail the use of isotope-edited NMR techniques and specific isotope labeling (with 15N, 13C) of the peptide. The overall goal of this work will be to obtain physical information regarding the specific recognition of antigen by antibodies in general. A more immediate and specific goal of this research will be to determine, using solution NMR techniques, how antigen specificity and virus neutralization differences among these anti-gp120 antibodies may be related to differences in the conformation adopted by this fifteen residue peptide when bound to these antibodies.
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