Evidence map›Paper›PMID 34917099›Full record

ArticleFrontiers in immunology2021

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

Klara Klein, Angelique Hölzemer, Tim Wang, Tae-Eun Kim, Haley L Dugan, Stephanie Jost, Marcus Altfeld, Wilfredo F Garcia-Beltran

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 7 institutions in 3 countries.

Klara KleinBroad Institute of MIT and Harvard, Cambridge, MA, United States.
Angelique HölzemerLeibniz Institute for Experimental Virology, Hamburg, Germany.
Tim WangBroad Institute of MIT and Harvard, Cambridge, MA, United States.
Tae-Eun KimRagon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Haley L DuganRagon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Stephanie JostRagon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Marcus AltfeldLeibniz Institute for Experimental Virology, Hamburg, Germany.
Wilfredo F Garcia-BeltranRagon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.
Leibniz Institute of Virology (LIV) · DEAdimab (United States) · USBeth Israel Deaconess Medical Center · USMassachusetts General Hospital · USMassachusetts Institute of Technology · USRagon Institute of MGH, MIT and Harvard · USUniversity of Veterinary Medicine Vienna · AT

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Vaccine Adjuvant/ Delivery Systems CoreP01AI104715 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI IRVINE, DARRELL J · 2013 to 2017
$12.3M
NK cell mediated immune pressure in HIV-1 infectionR01AI067031 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ALTFELD, MARCUS · 2006 to 2015
$4.4M
Identifying the ligand for the activating NK cell receptor KIR3DS1 and its protective role in HIV-1 disease progressionF31AI116366 · NIAID · HARVARD MEDICAL SCHOOL · PI GARCIA-BELTRAN, WILFREDO F · 2015 to 2018
$157k
NIAID NIH HHS F31 AI116366NIAID NIH HHS P01 AI104715NIAID NIH HHS R01 AI067031NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

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

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsGenome-Wide Association StudyHeparan Sulfate ProteoglycansHumansK562 CellsKiller Cells, NaturalLigandsReceptors, KIRReceptors, KIR3DS1Signal TransductionCRISPR-Associated Protein 9Heparan Sulfate ProteoglycansKIR3DS1 protein, humanLigandsReceptors, KIRReceptors, KIR3DS1CRISPRheparan sulfateKIRNK cellsscreen

Identifiers

PMID34917099
PMCPMC8669139
OpenAlexW3215056811

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.