An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function
- Zeinab Jame-Chenarboo
- Edward N. Schmidt
- Madeline Crichton
- Kei Takahashi-Yamashiro
- Guilherme M. Lima
- Liany Luna-Dulcey
- Jaesoo Jung
- Sabine Ivison
- Chris D. St. Laurent
- Jhon R. Enterina
- Sung-Yao Lin
- Susmita Sarkar
- Maju Joe
- Fahima Mozaneh
- Reni John
- Som G. Nanjappa
- Stacy A. Malaker
- Megan K. Levings
- Jamey D. Marth
- Ratmir Derda
- Matthew S. Macauley
2025-11-12
Siglecs are immunomodulatory receptors that regulate immune cell function. A fundamental challenge in studying Siglec-ligand interactions is the low affinity of Siglecs for their ligands. Inspired by how nature uses multivalency, we developed Siglec-liposomes as a highly multivalent and versatile platform for detecting Siglec glycan ligands in which recombinant Siglecs were conjugated to liposomes using the SpyCatcher-SpyTag system. Siglec-liposomes offer tunable multivalency and a modular assembly, enabling presentation of different Siglecs on the same liposome. Using Siglec-liposomes, we profiled Siglec ligands on human leukocytes, revealing distinct patterns of Siglec ligands. Moreover, Siglec-liposomes are in vivo compatible, where we demonstrated that Siglec-7–liposomes bind to the brain vasculature in a mucin domain–dependent manner. Given the abundance of Siglec ligands on T cells, we investigated whether Siglec-liposomes modulate T cell function and find that Siglec-7–liposomes increase T cell proliferation in an ST3Gal1-dependent and CD43-independent manner. Together, Siglec-liposomes are a versatile and sensitive tool for detecting Siglec ligands and immunomodulation.