Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 296, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jbc.2021.100477
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Funding
- Mizutani Foundation
- Daiko Foundation
- AMED [20ae0101069h0005]
- Academia Sinica Thematic Project Grant [AS-TP-108-ML06]
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The study identified leukosialin (CD43) as a counter-receptor for Siglec-7 on NK cells in regulating the cytotoxicity of NK cells towards K562 cells. The key role of a cluster of Sia-containing glycan epitopes on leukosialin as the trans-ligand for unmasking the cis-ligand was also demonstrated.
Sialic acid (Sia)-binding immunoglobulin-like lectin 7 (Siglec-7) is an inhibitory receptor primarily expressed on natural killer (NK) cells and monocytes. Siglec-7 is known to negatively regulate the innate immune system through Sia binding to distinguish self and nonself; however, a counter-receptor bearing its natural ligand remains largely unclear. Here, we identified a counter-receptor of Siglec-7 using K562 hematopoietic carcinoma cells presenting cell surface ligands for Siglec-7. We affinity-purified the ligands using Fc-ligated recombinant Siglec-7 and diSia-dextran polymer, a strong inhibitor for Siglec-7. We then confirmed the counter-receptor for Siglec-7 as leukosialin (CD43) through mass spectrometry, immunoprecipitation, and proximity labeling. Additionally, we demonstrated that the cytotoxicity of NK cells toward K562 cells was suppressed by overexpression of leukosialin in a Siglec-7-dependent manner. Taken together, our data suggest that leukosialin on K562 is a counter-receptor for Siglec-7 on NK cells and that a cluster of the Sia-containing glycan epitope on leukosialin is key as trans-ligand for unmasking the cis-ligand.
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