Abstract
Analysis of epitopes recognized by therapeutic monoclonal antibodies (mAb) is critical in clinical applications and in structure/function studies of target antigen. mAb MGr6 recognizes the extracellular domain of the p185HER2 oncoprotein and is a promising candidate for cancer immunodiagnosis and immunotherapy. Thus, epitope location and structure on p185HER2 need to be investigated. The use of MGr6-selected phage-displayed peptides for epitope analysis served to dissect the MGr6 epitope into at least two subregions, mimicked by CHSDC- and (L)P-(L)K(L) phage displayed peptides, respectively. Comparison of amino acid sequences of CHSDC peptides with the p185HER2 protein sequence and analysis of MGr6 reactivity with p185HER2 deletion mutants identified the linear subregion CCHEQCAAG of the MGr6 epitope, corresponding to amino acids 235-243 of the p185HER2 protein. This continuous subregion is part of a larger conformational epitope, and other amino acids, including a proline, a lysine and leucine residues contained in (L)P-(L)K(L) phage-displayed peptides appear to contribute to the formation of the MGr6 epitope surface.
References
Aug 1, 1978·Immunochemistry·M Z Atassi, J A Smith
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J K BatraC R King
Oct 1, 1991·Current Opinion in Biotechnology·G P Smith
Jul 6, 1992·Journal of Immunological Methods·B VojtĕsekD P Lane
Jun 1, 1992·Hybridoma·F CentisM I Colnaghi
Nov 20, 1991·Journal of Molecular Biology·F FeliciG Cesareni
Jul 1, 1995·Nature Medicine·M KatsumataM I Greene
Feb 1, 1993·International Journal of Cancer. Journal International Du Cancer·F XuR C Bast
Jun 15, 1993·Gene·A LuzzagoR Cortese
Oct 11, 1994·Gene·L DenteP Delmastro
Oct 15, 1994·International Journal of Cancer. Journal International Du Cancer·F J XuR C Bast
Apr 29, 1994·Journal of Medicinal Chemistry·M A GallopE M Gordon
Jul 20, 1993·Journal of Molecular Biology·B Rost, C Sander
Jul 15, 1996·European Journal of Biochemistry·D ParenteR De Santis
Citations
Mar 29, 2001·Molecular Immunology·T GazarianK Gazarian
Jul 6, 2000·Immunology Letters·K G GazarianJ P Laclette
Apr 12, 2000·European Journal of Biochemistry·C DemangelV Choumet
Apr 5, 2013·PloS One·Federico GabrielliAugusto Amici
Oct 24, 2003·Protein Science : a Publication of the Protein Society·Brian W BaileyEdward A Dratz
Mar 7, 2003·Molecular Cell·Thomas P J GarrettColin W Ward
Jul 15, 1999·International Journal of Cancer. Journal International Du Cancer·C M BoyerR C Bast
Jan 22, 2021·Journal of Virology·Maozhou HeNingshao Xia
Feb 13, 2001·Immunology Letters·N VaismanM Sela