Reply to Kascsak: Definition of the PrP 3F4 Epitope Revisited

Autor: Witold K. Surewicz, Man-Sun Sy, Shugui G. Chen, Qingzhong Kong, Piero Parchi, Jue Yuan, Xiangzhu Z. Xiao, Jan P. M. Langeveld, Edward Hoover, Hae-Eun Kang, Jian-Ping Guo, Patrick L. McGeer, Geoff Kneale, Gong-Xian Wang, Wen-Quan Zou, Neil S. Greenspan, John McGeehan, Glenn C. Telling, Mike C. Payne, David L. Kaplan
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Journal of Biological Chemistry, 285(20), le6-le6
Journal of Biological Chemistry 285 (2010) 20
ISSN: 0021-9258
Popis: This is a response to a letter by Kascsak (1) We appreciate the comments of Richard Kascsak on our new study (2) and regret the omission of a paper by him and co-workers (3) in our references. The fundamental importance of their work on the 3F4 antibody was recognized by our citation of two of their other relevant papers (4, 5). This reagent has greatly facilitated research on PrP and prion diseases. We fully agree with Dr. Kascsak that PrP residues Met109 and Met112 are contributory to the 3F4 epitope based on all observations including ours. We also offer the following responses to his other comments. Based on the absence of reactivity of 3F4 with 109MKHM112 and 107TNMKHM112 as observed by Lund et al. (6), we respectfully question whether TNMKHM is the “currently accepted” 3F4 epitope. We show that there is 3F4 immunoreactivity with 106KTNMK110 that lacks Met112 (2), suggesting that these 5 residues constitute a minimal 3F4 epitope. In the Rubenstein paper from 1999 (3), the KTNMK reactivity might have been missed since peptides were evaluated only with low 3F4 concentrations. Nevertheless, Lys106 proved to be a critical residue as evidenced by a marked reduction of 3F4 binding following its deletion in the 12-mer PrP peptide 107 (see Fig. 3 of Rubenstein et al. (3)), corroborating the conclusions of our study (2) as well as that of Lund et al. (6). While 3F4 remains the most important monoclonal antibody in studies of human prion diseases, our present findings suggest its suitability to monitor prion diseases in cervids as well.
Databáze: OpenAIRE