title: Dissection of the combining site in a humanized anti-Tac antibody.
abstract: The genetically engineered "humanized" anti-Tac antibody (HAT) has been shown to bind the p55 chain of the human IL-2R with an affinity close to that of the murine anti-Tac. Although the HAT molecule contains all six mouse CDR, it was not known which, and to what extent, each of the CDR contributes to Ag binding. These questions were addressed by constructing a series of variant HAT antibodies, each substituting a single HAT CDR with a heterologous CDR. The association constants of the variant HAT antibodies to p55 were determined by competitive binding analysis. We find that CDR 1 and 3 of the H chain and CDR 3 of the L chain are essential for maintaining binding. The remaining three CDR appear to be involved to a lesser degree.
authors.affiliation: Protein Design Labs, Inc., Mountain View, CA 94043.
authors.forename: S M
authors.initials: SM
authors.lastname: Glaser
authors.forename: M
authors.initials: M
authors.lastname: Vásquez
authors.forename: P W
authors.initials: PW
authors.lastname: Payne
authors.forename: W P
authors.initials: WP
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry*; D001666:Binding Sites, Antibody; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000276:immunology*
chemical_list: D000906:Antibodies; D007135:Immunoglobulin Variable Region; D015375:Receptors, Interleukin-2