20210226 Angata T Epub

Identification and functional characterization of a Siglec-7 counter-receptor on K562 cells

Identification and functional characterization of a Siglec-7 counter-receptor on K562 cells

J Biol Chem. Jan-Jun 2021; 296:100477. Epub 2021 Feb 26.
doi: 10.1016/j.jbc.2021.100477

閱讀文章

Yoshimura A, Asahina Y, Chang LY, Angata T, Tanaka H, Kitajima K, Sato C

摘要

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 non-self; however, a counter-receptor bearing its natural ligand remains largely unclear. Here, we identified the 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.