MOLECULAR-BASIS FOR THE BINDING PROMISCUITY OF AN ANTI-P24 (HIV-1) MONOCLONAL-ANTIBODY

Multiple binding capabilities utilized by specific protein-to-protein interactions in molecular recognition events are being documented incr easingly but remain poorly understood at the molecular level. We ident ified five unrelated peptides that compete with each other for binding to the paratope region of the monoclonal anti-p24 (HIV-1) antibody CB 4-1 by using a synthetic positional scanning combinatorial library XXX X[B-1,B-2,B-3,X-1,X-2,X-3]XXXX (14 mers; 68,590 peptide mixtures in to tal) prepared by spot synthesis. Complete sets of substitution analogs of the five peptides revealed key interacting residues, information t hat led to the construction of binding supertopes derived from each pe ptide. These supertope sequences were identified in hundreds of hetero logous proteins, and those proteins that could be obtained were shown to bind CB4-1. Implications of these findings for immune escape mechan isms and autoimmunity are discussed.