Epitope Mapping of Human Alpha-Fetoprotein

E. F. Yakimenko^*, A. K. Yazova, A. I. Goussev, and G. I. Abelev

Laboratory of Immunochemistry, Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, Moscow, 115478 Russia; fax: (095) 324-1205; E-mail: abelev@mx.iki.rssi.ru

^* To whom correspondence should be addressed.

Received July 27, 2000; Revision received December 20, 2000

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The epitope structure of human alpha-fetoprotein (AFP) was studied using more than 50 monoclonal antibodies (MAB) to human AFP. These MAB obtained from various world laboratories of the TD-2 AFP Workshops of the International Society for Oncodevelopmental Biology and Medicine (ISOBM-1996-1998-2000) were analyzed by competitive immunoaffinity electrochromatography (IAE) on nitrocellulose membranes (NCM). Five types of interaction of the AFP-MAB complex with the MAB fixed on NCM were found: 1) complete neutralization; 2) partial neutralization; 3) unidirectional neutralization; 4) enhanced binding; 5) lack of interaction. By IAE, 51 MAB were found to recognize 23 different epitopes in the AFP molecule. Based on these findings, an epitope map of AFP was designed which consists of eight epitope clusters and eight individual epitopes. The epitope location is considered with respect to the conformational state of the AFP molecule. Possible causes of the five types of interaction found on neutralization are discussed.

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KEY WORDS: alpha-fetoprotein, anti-alpha-fetoprotein monoclonal antibodies, alpha-fetoprotein epitopes, epitope mapping of alpha-fetoprotein, immunoaffinity electrochromatography

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