Parameters and determinants of responses to selection in antibody libraries

作者: Steven Schulz , Sébastien Boyer , Matteo Smerlak , Simona Cocco , Rémi Monasson

DOI: 10.1101/712539

关键词:

摘要: Antibody repertoires contain binders to nearly any target antigen. The sequences of these antibodies differ mostly at few sites located on the surface a scaffold that itself consists much less varied amino acids. What is impact this response selection repertoire? To gauge impact, we carried out quantitative phage display experiments with three antibody libraries based distinct scaffolds harboring same diversity randomized sites, which selected for binding four arbitrary targets. We first show an library captured by simple and measurable parameter direct physical information-theoretic interpretations. Second, identify major determinant encoded in scaffold, its degree evolutionary maturation. Antibodies undergo accelerated process, called affinity maturation, improve their given antigen as part adaptive immune response. find built around such maturated have lower other targets than naive germline origin. Our results are step towards quantifying controlling potential biomolecules.

参考文章(40)
Alexander M. Sevy, Tim M. Jacobs, James E. Crowe, Jens Meiler, Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences PLOS Computational Biology. ,vol. 11, pp. e1004300- ,(2015) , 10.1371/JOURNAL.PCBI.1004300
David Pressman, Alfred Nisonoff, Heterogeneity and average combining constants of antibodies from individual rabbits. Journal of Immunology. ,vol. 80, pp. 417- 428 ,(1958)
Anton Crombach, Paulien Hogeweg, Evolution of Evolvability in Gene Regulatory Networks PLoS Computational Biology. ,vol. 4, pp. e1000112- ,(2008) , 10.1371/JOURNAL.PCBI.1000112
D. Lancet, E. Sadovsky, E. Seidemann, Probability model for molecular recognition in biological receptor repertoires: significance to the olfactory system. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 3715- 3719 ,(1993) , 10.1073/PNAS.90.8.3715
I. F. Thorpe, C. L. Brooks, Molecular evolution of affinity and flexibility in the immune system Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 8821- 8826 ,(2007) , 10.1073/PNAS.0610064104
Jordan R. Willis, Bryan S. Briney, Samuel L. DeLuca, James E. Crowe, Jens Meiler, Human Germline Antibody Gene Segments Encode Polyspecific Antibodies PLoS Computational Biology. ,vol. 9, pp. e1003045- ,(2013) , 10.1371/JOURNAL.PCBI.1003045
Eynat Dellus-Gur, Agnes Toth-Petroczy, Mikael Elias, Dan S. Tawfik, What makes a protein fold amenable to functional innovation? fold polarity and stability trade-offs Journal of Molecular Biology. ,vol. 425, pp. 2609- 2621 ,(2013) , 10.1016/J.JMB.2013.03.033
Gary J Wedemayer, Phillip A Patten, Leo H Wang, Peter G Schultz, Raymond C Stevens, Structural Insights into the Evolution of an Antibody Combining Site Science. ,vol. 276, pp. 1665- 1669 ,(1997) , 10.1126/SCIENCE.276.5319.1665