Synthetic nanobodies as tools to distinguish IgG Fc glycoforms.
| Publication Type | Academic Article |
| Authors | Kao K, Gupta A, Zong G, Li C, Kerschbaumer I, Borghi S, Achkar J, Bournazos S, Wang L, Ravetch J |
| Journal | Proc Natl Acad Sci U S A |
| Volume | 119 |
| Issue | 48 |
| Pagination | e2212658119 |
| Date Published | 11/21/2022 |
| ISSN | 1091-6490 |
| Keywords | Single-Domain Antibodies, COVID-19 |
| 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. |
| DOI | 10.1073/pnas.2212658119 |
| PubMed ID | 36409896 |
| PubMed Central ID | PMC9860306 |