A Coarse-Grained Model of Affinity Maturation Indicates the Importance of B-Cell Receptor Avidity in Epitope Subdominance.

ABSTRACT: The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal in the design of vaccines against rapidly-mutating viruses. In the case of influenza, many bnAbs that target conserved epitopes on the stem of the hemagglutinin protein (HA) have been discovered. However, these antibodies are rare, are not boosted well upon reinfection, and often have low neutralization potency, compared to strain-specific antibodies directed to the HA head. Different hypotheses have been proposed to explain this phenomenon. We use a coarse-grained computational model of the germinal center reaction to investigate how B-cell receptor binding valency affects the growth and affinity maturation of competing B-cells. We find that receptors that are unable to bind antigen bivalently, and also those that

SUBMITTER: Ovchinnikov V 

PROVIDER: S-EPMC8971376 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature