Topographic Analysis with Monoclonal Anti-Idiotopes: Probing the Functional Anatomy of Immunoglobulin Variable Domains

Abstract

Attempts to correlate immunoglobulin variable domain functional properties with variable domain primary structure have been valuable, but these efforts have suggested that to more fully account for variable domain function in terms of structure will require knowledge of molecular relationships in three dimensions. In this review we describe generally applicable methods, using monoclonal anti-idiotopes, for the determination of spatial relationships of idiotopes relative to one another and relative to two orienting structural markers of variable domains: 1) the hapten-binding site and 2) the junction of the variable and constant domains. Using these methods it has been possible to construct an oriented idiotope map which spans the variable domain along an axis connecting the paratope and the variable domain-constant domain junction. In addition, it has been possible to correlate idiotope position with other properties of idiotope expression. This approach may contribute to the development of predictive principles of idiotope expression.