Structural features of the interaction between an anti-clonotypic antibodyand its cognate T-cell antigen receptor

The crystal structure of the complex between a single chain Fv fragment of the KB5-C20 T-cell antigen receptor (TCR) and the specific anti-clonotypic antibody (Ab) Desire-1 provides the first description of the interface betw een a clonotype and an anti-clonotype. Ln the four idiotype/anti-idiotype c omplexes of known three-dimensional structures, the interacting Fv fragment s associate largely through their complementarity-determining regions (CDRs ). in marked contrast, Desire-1 binds to a face of the KB5-C20 TCR that is almost perpendicular to the TCR antigen binding site, and recognizes discon tinuous stretches of TCR V alpha and V beta residues that belong to both th e CDRs and the framework. Despite this peculiar mode of interaction, Desire -1 constitutes a genuine anti-clonotypic Ab. Moreover, in spite of the fact that the Desire-1 contact residues do not constitute a molecular mimic of the physiological ligand normally recognized by the KB5-C20 TCR, the bivale nt Desire-1 Ab is capable of efficiently activating T-cells expressing the KB5-C20 TCR. (C) 1999 Academic Press.