On the specificity of antibody/antigen interactions: phosphocholine binding to McPC603 and the correlation of three-dimensional structure and sequence data.
Refined three-dimensional structures of McPC603 Fab and the complex with phosphocholine permit a detailed assessment of the residues crucial to determining the antibody specificity. Correlation with sequence data suggests that the structure of the binding site is highly conserved in immunoglobulins with phosphocholine-binding specificity. There is suggestive evidence that coupling of somatic mutations occurs to preserve antigen-binding specificity. The immune response is characterized by specificity and diversity. While each antibody appears to be specific for a single antigen, the immune response can generate up to 10(9) different specificities. In order to understand, at the molecular level, the nature of the interaction between antibody and antigen, it is necessary to have a high-resolution three-dimensional picture of the complex. Today it is possible to investigate antibody/antigen interactions directly by the crystallographic analysis of hybridoma products [5, 10]; in the past, structural studies were limited to myeloma proteins which, in some cases, could be shown to complex to certain haptens. Of the four Fab structures that have been determined by X-ray diffraction, only two have been demonstrated to bind hapten in the crystal. They are Fab NEW, which was shown to bind a vitamin K1 derivative [1] and McPC603, which binds to phosphocholine [6,9]. During the last few years, the McPC603 Fab structure has been refined at 2.7 A resolution and the complex of McPC603 Fab with phosphocholine has been refined independently at 3.1 A. In this communication, we make a comparative analysis of the sequences of a number of mouse phosphocholine-binding immunoglobulins based on the refined structure of the phosphocholine-binding site in McPC603.
D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D001665:Binding Sites; D002460:Cell Line; D002794:Choline / Q000031:analogs & derivatives*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D008958:Models, Molecular; D010767:Phosphorylcholine / Q000378:metabolism*; D014961:X-Ray Diffraction
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D010767:Phosphorylcholine; D002794:Choline