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

Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (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.

Autoren:   Katharina Imkeller; Stephen 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
Journal:   Science
Band:   360
Ausgabe:   6395
Jahrgang:   2018
Seiten:   1358
DOI:   10.1126/science.aar5304
Erscheinungsdatum:   22.06.2018
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