Featured Poster: Retrospective structural analysis of affinity maturation from a semi-synthetic library
Featured Presenter: Joseph Arndt, Biogen Idec
About the Poster: The immune system responds to foreign antigens by rapid affinity maturation of
germline antibodies with increasing affinity for antigens. Prior studies reveal that the maturation process is achieved, in part, by prearranging and rigidifying the CDRs for antigen binding via cycles of somatic hypermutation and selection. Mature CDRs are arranged in a small subset of canonical structures in five of the six CDR loops that define the antigen-binding site. How affinity mutations modulate CDR structure in man-made in vitro display systems is less clear. Here, we structurally probe five semi-synthetic antibodies with and without antigen at different stages of the affinity maturation by X-ray crystallography and point mutation modeling. These molecular snapshots reveal no evidence of CDR rigidification, but rather reveal non-canonical CDR structural conformations and induced fit conformational changes in the CDRs upon antigen binding. These findings suggest a possible link between CDR flexibility and non-specificity, which is more common in antibodies isolated from in vitro systems, and may enable rational engineering of antibodies for improved affinity.
Do you have new research to share with your industry colleagues? Your poster can be featured in the Antibody Engineering Exhibit hall as well! Find out how here. The deadline for poster submissions is November 1.
Share this article with your social network, just click below to share now!
|
|
No comments :
Post a Comment