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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope
Science, Volume 360, No. 6395, Year 2018
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Description
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. © 2017 The Authors.,
Authors & Co-Authors
Scally, Stephen W.
Canada, Toronto
Sickkids Research Institute
Bosch, Alexandre
Canada, Toronto
Sickkids Research Institute
Costa, Giulia
Germany, Berlin
Max Planck Institute for Infection Biology
Triller, Gianna
Germany, Heidelberg
German Cancer Research Center
Murugan, Rajagopal
Germany, Heidelberg
German Cancer Research Center
Jumaa, Hassan
Germany, Ulm
Universitätsklinikum Ulm
Kremsner, Peter G.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Kim Lee Sim, Betty
United States, Rockville
Sanaria Inc.
Hoffman, Stephen L.
United States, Rockville
Sanaria Inc.
Mordmüller, Benjamin G.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Levashina, Elena A.
Germany, Berlin
Max Planck Institute for Infection Biology
Julien, Jean Philippe
Canada, Toronto
Sickkids Research Institute
Canada, Toronto
University of Toronto
Wardemann, Hedda
Germany, Heidelberg
German Cancer Research Center
Statistics
Citations: 67
Authors: 13
Affiliations: 8
Identifiers
Doi:
10.1126/science.aar5304
ISSN:
00368075
Research Areas
Infectious Diseases