Research ArticleANTIBODIES

Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies

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Science Immunology  14 Jul 2016:
Vol. 1, Issue 1, pp. aaf7962
DOI: 10.1126/sciimmunol.aaf7962

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“Stalk”ing the antigen

Engineers frequently look to nature for inspiration. Antibody engineers are no exception, modeling new therapeutics on molecules found in animals such as camels and cows. Indeed, 10% of bovine antibodies have unusually long heavy-chain CDR3s as part of their antigen-recognition sites. Stanfield et al. have solved crystal structures of three new bovine Fab fragments and analyzed the five known structures to show that their ultralong CDR H3s all adopt similar architectures composed of a knob domain containing a small conserved β-sheet connected by diverse disulfide-bonded loops that is separated from the antibody surface by a long conserved stalk. They propose that varying the length of the stalk and the positions and number of disulfides in the knob may help drive antibody diversity. These structural insights could be leveraged to tailor antibody-based therapeutics.