RT Journal Article
SR Electronic
T1 Parameters and determinants of responses to selection in antibody libraries
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 712539
DO 10.1101/712539
A1 Steven Schulz
A1 Sébastien Boyer
A1 Matteo Smerlak
A1 Simona Cocco
A1 Rémi Monasson
A1 Clément Nizak
A1 Olivier Rivoire
YR 2019
UL http://biorxiv.org/content/early/2019/07/23/712539.abstract
AB Antibody repertoires contain binders to nearly any target antigen. The sequences of these antibodies differ mostly at few sites located on the surface of a scaffold that itself consists of much less varied amino acids. What is the impact of this scaffold on the response to selection of a repertoire? To gauge this impact, we carried out quantitative phage display experiments with three antibody libraries based on distinct scaffolds harboring the same diversity at randomized sites, which we selected for binding to four arbitrary targets. We first show that the response to selection of an antibody library is captured by a simple and measurable parameter with direct physical and information-theoretic interpretations. Second, we identify a major determinant of this parameter which is encoded in the scaffold, its degree of evolutionary maturation. Antibodies undergo an accelerated evolutionary process, called affinity maturation, to improve their affinity to a given target antigen as part of the adaptive immune response. We find that libraries of antibodies built around such maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around naïve scaffolds of germline origin. Our results are a first step towards quantifying and controlling the evolutionary potential of biomolecules.