Summary
A subset of mutations contribute disproportionately to affinity (1,2). Using yeast display, Kirby et al(2) found that most mutations obtained during affinity maturation have no impact on affinity. These may have instead been selected to lower self-association to other human proteins.
See also
1.
Julian MC, Li L, Garde S, Wilen R, Tessier PM. Efficient affinity maturation of antibody variable domains requires co-selection of compensatory mutations to maintain thermodynamic stability. Scientific Reports. 2017;7(1). Available from: https://doi.org/10.1038/srep45259
2.
Kirby MB, Petersen BM, Faris JG, Kells SP, Sprenger KG, Whitehead TA. Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive. Proceedings of the National Academy of Sciences. 2025;122(4). Available from: https://doi.org/10.1073/pnas.2412787122