Universal characterization of epitope immunodominance from a multi-scale model of clonal competition in germinal centers
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| Format: | Preprint |
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2023
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| _version_ | 1866929230568226816 |
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| author | Ferretti, Federica Kardar, Mehran |
| author_facet | Ferretti, Federica Kardar, Mehran |
| contents | We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal 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 multi-scale 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 construct an effective \emph{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 identify general principles for the rational design of two-antigen cocktails. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2310_10966 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | Universal characterization of epitope immunodominance from a multi-scale model of clonal competition in germinal centers Ferretti, Federica Kardar, Mehran Populations and Evolution Statistical Mechanics Biological Physics We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal 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 multi-scale 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 construct an effective \emph{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 identify general principles for the rational design of two-antigen cocktails. |
| title | Universal characterization of epitope immunodominance from a multi-scale model of clonal competition in germinal centers |
| topic | Populations and Evolution Statistical Mechanics Biological Physics |
| url | https://arxiv.org/abs/2310.10966 |