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Updated: Jun 20, 2025

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Universal characterization of epitope immunodominance from a multiscale model of clonal competition in germinal

Federica Ferretti1, Mehran Kardar2

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Physical Review. E
|July 18, 2024
PubMed

We introduce a multiscale model for affinity maturation, which aims to capture the intraclonal, interclonal, and epitope-specific organization of the B-cell population in a germinal center. We describe the evolution of the B-cell population via a quasispecies dynamics, with species corresponding to unique B-cell receptors (BCRs), where the desired multiscale structure is reflected on the mutational connectivity of the accessible BCR space, and on the statistical properties of its fitness landscape. Within this mathematical framework, we study the competition among classes of BCRs targeting different antigen epitopes, and we construct an effective immunogenic space where epitope immunodominance relations can be universally characterized. We finally study how varying the relative composition of a mixture of antigens with variable and conserved domains allows for a parametric exploration of this space, and we identify general principles for the rational design of two-antigen cocktails.

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