Identification of the core residues of the epitope of a monoclonal antibody raised against glycoprotein D of herpes simplex virus type 1 by screening of a random peptide library

Gerard A. Schellekens*, Edwin Lasonder, Matty Feijlbrief, Danny G.A.M. Koedijk, Jan Wouter Drijfhout, Albert‐Jan ‐J Scheffer, Sytske Welling‐Wester, Gjalt W. Welling

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Random peptide libraries (RPL) displayed on the surface of a filamentous bacteriophage can be used to identify peptide ligands that interact with target molecules. We have used a 15‐amino acid residue RPL displayed on bacteriophage M13 to identify the core residues within the epitope of a monoclonal antibody (mAb) A16 which interacts with a continuous epitope restricted to amino acid residues 9 to 19 in the N‐terminal region of glycoprotein D of herpes simplex virus type 1 (gD‐1). The single peptide sequence obtained after three rounds of selection contained identical residues at three positions compared to the authentic gD‐1 sequence. Synthetic peptides were prepared based on the sequence of the original epitope and the phage‐derived epitope. The binding constants (Ka) with mAb A16 were determined using surface plasmon resonance (SPR) biosensor technology. The RPL‐derived peptide and peptide 9–19 of gD‐1 had approximately the same affinity for mAb A16. This suggests that those residues within the epitope that are essential for binding were identified. The synthesis of shorter versions of the RPL‐derived peptide restricted the binding region to seven amino acid residues. These results show that minimal information retrieved from the screening of an RPL combined with peptide synthesis can characterize the epitope of an mAb with high resolution. Immunization of mice with the phage‐derived peptide protected against a challenge with a lethal dose of herpes simplex virus type 1 equally well as the gD‐1 derived peptide.

Original languageEnglish
Pages (from-to)3188-3193
Number of pages6
JournalEuropean Journal of Immunology
Volume24
Issue number12
DOIs
Publication statusPublished - 1 Dec 1994
Externally publishedYes

Fingerprint Dive into the research topics of 'Identification of the core residues of the epitope of a monoclonal antibody raised against glycoprotein D of herpes simplex virus type 1 by screening of a random peptide library'. Together they form a unique fingerprint.

Cite this