A Genome-Wide CRISPR/Cas9-Based Screen Identifies Heparan Sulfate Proteoglycans as Ligands of Killer-Cell Immunoglobulin-Like Receptors.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2021
Historique:
received: 19 10 2021
accepted: 11 11 2021
entrez: 17 12 2021
pubmed: 18 12 2021
medline: 1 3 2022
Statut: epublish

Résumé

While human leukocyte antigen (HLA) and HLA-like proteins comprise an overwhelming majority of known ligands for NK-cell receptors, the interactions of NK-cell receptors with non-conventional ligands, particularly carbohydrate antigens, is less well described. We previously found through a bead-based HLA screen that KIR3DS1, a formerly orphan member of the killer-cell immunoglobulin-like receptor (KIR) family, binds to HLA-F. In this study, we assessed the ligand binding profile of KIR3DS1 to cell lines using Fc fusion constructs, and discovered that KIR3DS1-Fc exhibited binding to several human cell lines including ones devoid of HLA. To identify these non-HLA ligands, we developed a magnetic enrichment-based genome-wide CRISPR/Cas9 knock-out screen approach, and identified enzymes involved in the biosynthesis of heparan sulfate as crucial for the binding of KIR3DS1-Fc to K562 cells. This interaction between KIR3DS1 and heparan sulfate was confirmed

Identifiants

pubmed: 34917099
doi: 10.3389/fimmu.2021.798235
pmc: PMC8669139
doi:

Substances chimiques

Heparan Sulfate Proteoglycans 0
KIR3DS1 protein, human 0
Ligands 0
Receptors, KIR 0
Receptors, KIR3DS1 0
CRISPR-Associated Protein 9 EC 3.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

798235

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI067031
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI104715
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI116366
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States

Informations de copyright

Copyright © 2021 Klein, Hölzemer, Wang, Kim, Dugan, Jost, Altfeld and Garcia-Beltran.

Déclaration de conflit d'intérêts

Author HD is employed by Adimab, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Klara Klein (K)

Broad Institute of MIT and Harvard, Cambridge, MA, United States.
Whitehead Institute for Biomedical Research, Cambridge, MA, United States.
Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.

Angelique Hölzemer (A)

Leibniz Institute for Experimental Virology, Hamburg, Germany.
First Department of Internal Medicine, Division of Infectious Diseases, University Medical Centre Eppendorf, Hamburg, Germany.
German Center for Infection Research (DZIF), Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.

Tim Wang (T)

Broad Institute of MIT and Harvard, Cambridge, MA, United States.
Whitehead Institute for Biomedical Research, Cambridge, MA, United States.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States.

Tae-Eun Kim (TE)

Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.

Haley L Dugan (HL)

Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Adimab, LLC, Lebanon, NH, United States.

Stephanie Jost (S)

Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States.

Marcus Altfeld (M)

Leibniz Institute for Experimental Virology, Hamburg, Germany.

Wilfredo F Garcia-Beltran (WF)

Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Department of Pathology, Massachusetts General Hospital (MGH), Boston, MA, United States.

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