Neoepitope antibodies against MMP-cleaved and aggrecanase-cleaved aggrecan.

Abstract

Neoepitope antibodies recognize the newly created N or C terminus of protein degradation products but fail to recognize the same sequence of amino acids present in intact or undigested protein. Aggrecan neoepitope antibodies have been pivotal in studies determining the contribution of matrix metalloproteinases (MMPs) and aggrecanases to aggrecanolysis. In particular, an antibody to the A(374)RGSV N terminus was instrumental in the landmark discovery of the aggrecanases, ADAMTS-4 and ADAMTS-5. Antibodies to neoepitopes at the major MMP cleavage site DIPEN(341)/(342)FFGVG helped to distinguish MMP-driven aggrecan loss from aggrecanase-driven aggrecan loss and idenepsied a role for MMPs in late..