Synthetic nanobodies as tools to distinguish IgG Fc glycoforms.
Proc Natl Acad Sci U S A
; 119(48): e2212658119, 2022 Nov 29.
Article
in English
| MEDLINE | ID: covidwho-2265470
ABSTRACT
Protein glycosylation is a crucial mediator of biological functions and is tightly regulated in health and disease. However, interrogating complex protein glycoforms is challenging, as current lectin tools are limited by cross-reactivity while mass spectrometry typically requires biochemical purification and isolation of the target protein. Here, we describe a method to identify and characterize a class of nanobodies that can distinguish glycoforms without reactivity to off-target glycoproteins or glycans. We apply this technology to immunoglobulin G (IgG) Fc glycoforms and define nanobodies that specifically recognize either IgG lacking its core-fucose or IgG bearing terminal sialic acid residues. By adapting these tools to standard biochemical methods, we can clinically stratify dengue virus and SARS-CoV-2 infected individuals based on their IgG glycan profile, selectively disrupt IgG-Fcγ receptor binding both in vitro and in vivo, and interrogate the B cell receptor (BCR) glycan structure on living cells. Ultimately, we provide a strategy for the development of reagents to identify and manipulate IgG Fc glycoforms.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Single-Domain Antibodies
/
COVID-19
Type of study:
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Proc Natl Acad Sci U S A
Year:
2022
Document Type:
Article
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