Journal article

A LAIR-1 insertion creates broadly reactive antibodies against malaria variant antigens

  • Tan, Joshua Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya - Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK
  • Pieper, Kathrin Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Piccoli, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Abdi, Abdirahman KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya
  • Tully, Claire Maria KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya
  • Foglierini Perez, Mathilde Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Geiger, Roger Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Switzerland
  • Jarrossay, David Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Maina Ndungu, Francis KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya
  • Wambua, Juliana KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya
  • Bejon, Philip KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya - Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK
  • Silacci Fregni, Chiara : Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Fernandez-Rodriguez, Blanca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Barbieri, Sonia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Bianchi, Siro Humabs BioMed SA, Bellinzona, Switzerland
  • Marsh, Kevin KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya - Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK
  • Thathy, Vandana KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya
  • Corti, Davide Humabs BioMed SA, Bellinzona, Switzerland
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Bull, Peter KEMRI-Wellcome Trust Research Programme, CGMRC, Kilifi, Kenya - Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Switzerland
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    23.12.2015
Published in:
  • Nature. - 2016, vol. 529, p. 25 p
English Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies1,2,3,4. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 98 amino acid collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B-cell clone and carry distinct somatic mutations in the LAIR1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319353
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