Synthetic nanobodies as tools to distinguish IgG Fc glycoforms.

TitleSynthetic nanobodies as tools to distinguish IgG Fc glycoforms.
Publication TypeJournal Article
Year of Publication2022
AuthorsKao KS, Gupta A, Zong G, Li C, Kerschbaumer I, Borghi S, Achkar JM, Bournazos S, Wang L-X, Ravetch JV
JournalProc Natl Acad Sci U S A
Date Published2022 Nov 29
KeywordsCOVID-19, Humans, Immunoglobulin Fc Fragments, Immunoglobulin G, Polysaccharides, SARS-CoV-2, Single-Domain Antibodies

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.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID36409896

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