Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope

Authors: Katharina Imkeller, S.W. Scally, Alexandre Bosch, Gemma Pidelaserra-Martí, Giulia Costa, Gianna Triller, Rajagopal Murugan, Valerio Renna, Hassan Jumaa, Peter G. Kremsner, B. Kim Lee Sim, Stephen L. Hoffman, Benjamin Mordmüller, Elena A. Levashina, Jean‐Philippe Julien, Hedda Wardemann - Science 2018 cited by 127

(PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens.