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dc.contributor.author
Chen, Yiwei
dc.contributor.author
Xu, Kai
dc.contributor.author
Piccoli, Luca
dc.contributor.author
Foglierini, Mathilde
dc.contributor.author
Tan, Joshua
dc.contributor.author
Jin, Wenjie
dc.contributor.author
Gorman, Jason
dc.contributor.author
Tsybovsky, Yaroslav
dc.contributor.author
Zhang, Baoshan
dc.contributor.author
Traore, Boubacar
dc.contributor.author
Silacci-Fregni, Chiara
dc.contributor.author
Daubenberger, Claudia A.
dc.contributor.author
Crompton, Peter D.
dc.contributor.author
Geiger, Roger
dc.contributor.author
Sallusto, Federica
dc.contributor.author
Kwong, Peter D.
dc.contributor.author
Lanzavecchia, Antonio
dc.date.accessioned
2021-05-07T07:11:14Z
dc.date.available
2021-05-05T04:03:20Z
dc.date.available
2021-05-07T07:11:14Z
dc.date.issued
2021-04-22
dc.identifier.issn
0028-0836
dc.identifier.issn
1476-4687
dc.identifier.other
10.1038/s41586-021-03378-6
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/482463
dc.description.abstract
Some Plasmodium falciparum repetitive interspersed families of polypeptides (RIFINs)—variant surface antigens that are expressed on infected erythrocytes —bind to the inhibitory receptor LAIR1, and insertion of DNA that encodes LAIR1 into immunoglobulin genes generates RIFIN-specific antibodies . Here we address the general relevance of this finding by searching for antibodies that incorporate LILRB1, another inhibitory receptor that binds to β2 microglobulin and RIFINs through their apical domains . By screening plasma from a cohort of donors from Mali, we identified individuals with LILRB1-containing antibodies. B cell clones isolated from three donors showed large DNA insertions in the switch region that encodes non-apical LILRB1 extracellular domain 3 and 4 (D3D4) or D3 alone in the variable–constant (VH–CH1) elbow. Through mass spectrometry and binding assays, we identified a large set of RIFINs that bind to LILRB1 D3. Crystal and cryo-electron microscopy structures of a RIFIN in complex with either LILRB1 D3D4 or a D3D4-containing antibody Fab revealed a mode of RIFIN–LILRB1 D3 interaction that is similar to that of RIFIN–LAIR1. The Fab showed an unconventional triangular architecture with the inserted LILRB1 domains opening up the VH–CH1 elbow without affecting VH–VL or CH1–CL pairing. Collectively, these findings show that RIFINs bind to LILRB1 through D3 and illustrate, with a naturally selected example, the general principle of creating novel antibodies by inserting receptor domains into the VH–CH1 elbow. 1 2,3 4,5
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.subject
Antibodies
en_US
dc.subject
class switch recombination
en_US
dc.subject
Malaria
en_US
dc.title
Structural basis of malaria RIFIN binding by LILRB1-containing antibodies
en_US
dc.type
Journal Article
dc.date.published
2021-03-31
ethz.journal.title
Nature
ethz.journal.volume
592
en_US
ethz.journal.issue
7855
en_US
ethz.pages.start
639
en_US
ethz.pages.end
643
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::09604 - Sallusto, Federica / Sallusto, Federica
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::09604 - Sallusto, Federica / Sallusto, Federica
ethz.date.deposited
2021-05-05T04:03:41Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2021-05-07T07:11:23Z
ethz.rosetta.lastUpdated
2022-03-29T07:08:50Z
ethz.rosetta.versionExported
true
ethz.COinS
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