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Journal of Virology, July 2001, p. 6692-6699, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6692-6699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification and Characterization of a Peptide That Specifically Binds the Human, Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody b12

Michael B. Zwick,1,dagger Lori L. C. Bonnycastle,1,Dagger Alfredo Menendez,1 Melita B. Irving,1 Carlos F. Barbas III,2 Paul W. H. I. Parren,3 Dennis R. Burton,2,3 and Jamie K. Scott1,*

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada,1 and Departments of Molecular Biology2 and Immunology,3 The Scripps Research Institute, La Jolla, California 92037

Received 16 October 2000/Accepted 15 April 2001

Human monoclonal antibody (MAb) b12 recognizes a conformational epitope that overlaps the CD-4-binding site of the human immunodeficiency virus type 1 (HIV-1) envelope. MAb b12 neutralizes a broad range of HIV-1 primary isolates and protects against primary virus challenge in animal models. We report here the discovery and characterization of B2.1, a peptide that binds specifically to MAb b12. B2.1 was selected from a phage-displayed peptide library by using immunoglobulin G1 b12 as the selecting agent. The peptide is a homodimer whose activity depends on an intact disulfide bridge joining its polypeptide chains. Competition studies with gp120 indicate that B2.1 occupies the b12 antigen-binding site. The affinity of b12 for B2.1 depends on the form in which the peptide is presented; b12 binds best to the homodimer as a recombinant polypeptide fused to the phage coat. Originally, b12 was isolated from a phage-displayed Fab library constructed from the bone marrow of an HIV-1-infected donor. The B2.1 peptide is highly specific for b12 since it selected only phage bearing b12 Fab from this large and diverse antibody library.

* Corresponding author. Mailing address: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr., Burnaby, British Columbia V5A 1S6, Canada. Phone: (604) 291-5658. Fax: (604) 291-5583. E-mail: jkscott{at}sfu.ca.

dagger Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037.

Dagger Present address: Monsanto Corp., Ankeny, IA 50021.

Journal of Virology, July 2001, p. 6692-6699, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6692-6699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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