Antibodies - two for one

Antibodies have an exquisite specificity but are also able to cross react with multiple antigens. Specificity is achieved by clonal expansion, but the molecular mechanisms of multispecificity have been unclear. In the February 28 Science, Leo C. James and colleagues at the MRC Centre for Protein Engineering, Cambridge, UK, show that antibody multispecificity can be mediated by conformational diversity of preexisting isomers that can adopt multiple functions and can increase the effective size of the antibody repertoire (Science, 299:1362-1367, February 28, 2003).

James et al. analyzed the antibody SPE7 (a monoclonal immunoglobulin E (IgE) raised against a 2,4-dinitrophenyl hapten) using x-ray crystallography and pre–steady-state kinetics. They observed that SPE7 adopted at least two different preexisting conformations that were independent of antigen, each conferring a different antigen-binding function. In addition, they showed that a protein antigen made use of an unrelated antibody isomer with a wide, shallow binding site.

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