Tan, Joshua Pieper, Kathrin Piccoli, Luca Abdi, Abdirahman Tully, Claire Maria Foglierini Perez, Mathilde Geiger, Roger Jarrossay, David Maina Ndungu, Francis Wambua, Juliana Bejon, Philip Silacci Fregni, Chiara : Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland Fernandez-Rodriguez, Blanca Barbieri, Sonia Bianchi, Siro Marsh, Kevin Thathy, Vandana Corti, Davide Sallusto, Federica Bull, Peter Lanzavecchia, Antonio 2015-12-23 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. application/pdf https://susi.usi.ch/global/documents/319353 https://localhost:5000/ark:/12658/srd1319353 https://susi.usi.ch/documents/319353/files/Tan_2020_nature.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/nature16450 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319353 info:eu-repo/semantics/openAccess License undefined Nature. - 2016, vol. 529, p. 25 p info:eu-repo/classification/udc/61 A LAIR-1 insertion creates broadly reactive antibodies against malaria variant antigens http://purl.org/coar/resource_type/c_6501