The class
A neutralizing antibody's epitope maps to CETP's C-terminal lipid-binding region, revealing its inhibition mechanism (J Biol Chem 1989)
Original title: Mechanism of cholesteryl ester transfer protein inhibition by a neutralizing monoclonal antibody and mapping of the monoclonal antibody epitope
The 74,000 Da CETP has a neutral lipid binding site that equilibrates with lipoprotein cholesteryl esters and triglycerides. Researchers localized the epitope of the neutralizing monoclonal antibody TP2 to a hydrophobic 26-amino acid sequence at CETP's carboxy terminus. TP2 Fab fragments caused partial (50%) inhibition of cholesteryl ester transfer but complete inhibition of triglyceride transfer, reduced cholesteryl ester binding to CETP by 37%, and abolished triglyceride binding entirely, while unexpectedly enhancing CETP's binding to plasma lipoproteins and phospholipid vesicles. The findings indicate TP2 inhibits lipid transfer by blocking lipid uptake into a COOH-terminal binding site, occupancy of which may trigger a conformational change that increases CETP's affinity for lipoproteins and vesicles.
Original abstract
The plasma cholesteryl ester transfer protein (CETP, Mr 74,000) has a binding site for neutral lipid which can readily equilibrate with lipoprotein cholesteryl esters or triglycerides. Recently, a monoclonal antibody (TP2) was obtained which neutralizes the cholesteryl ester (CE) and triglyceride (TG) transfer activities of the CETP. In this report, the epitope of the inhibitory monoclonal antibody has been localized to a hydrophobic 26-amino acid sequence at the COOH terminus of CETP. The Fab fragments of TP2 caused partial (50%) inhibition of CE transfer and complete inhibition of TG transfer by the CETP. Similarly, the Fab fragments inhibited (37%) the binding of CE to the CETP and abolished the binding of TG to the CETP. Surprisingly, the TP2 Fab was also found to enhance the binding of CETP to plasma lipoproteins and to phospholipid vesicles. In conclusion, the TP2 monoclonal antibody inhibits lipid transfer by blocking the uptake of lipid by CETP. The COOH-terminal epitope may be in or near the neutral lipid binding site. Occupancy of this site by TP2 Fab fragments or by neutral lipid may result in a conformational change of CETP causing enhanced binding to lipoproteins or vesicles.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.