Journal
NATURE
Volume 529, Issue 7584, Pages 105-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature16450
Keywords
-
Categories
Funding
- European Research Council [250348, 670955]
- Swiss National Science Foundation [160279]
- Swiss Vaccine Research Institute
- Wellcome Trust [084535, 077092, 084538, 084113/Z/07/Z, 084378/Z/07/A, 092741, 099811]
- Helmut Horten Foundation
- Wellcome Trust [084113/Z/07/Z, 084378/Z/07/A] Funding Source: Wellcome Trust
- Medical Research Council [G1002624] Funding Source: researchfish
- European Research Council (ERC) [250348, 670955] Funding Source: European Research Council (ERC)
- MRC [G1002624] Funding Source: UKRI
Ask authors/readers for more resources
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 antibodies(1-4). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available