Accommodation of Mutations in Antigen-Antibody Interfaces

Alanine-scanning mutagenesis of the D1.3-HEL interface has demonstrated that it is remarkably tolerant to mutations that, on the basis of the three-dimensional structure of the wild-type complex, might be expected to have pronounced effects on affinity (DaU Acqua et al., 1998). For example, truncation of HEL residue Asp-18 to alanine should result in the loss of a direct hydrogen bond to the side chain of D 1.3 VLTyr-50 (Asp-18HEL 082-0ri D1.3 VLTyr-50), as well as the loss of seven van der Waals contacts to this residue. Nevertheless, the affinity of HEL D18Afor D1.3 (4.5 X lO M ) is nearly identical to that of the wild-type 

Functional Roles for Protein Plasticity in Antigen Recogntion 

Most mature antibodies have affinities for their speciflc antigens in the range of 10 —10 M and it has been proposed (Foote and Eisen, 1995) that, due to diffusion rates and the residence time required for antibody internalization controlling on- and off-rates, an affinity ceiling exists for antibody-antigen interactions of approximately lO Antibodies with 

Washington University Schooi of Medicine, St. Louis, Missouri 63110 

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