Deficiency of N-linked glycosylation impairs immune function of B7-H6

Hanqing Chen; Hanqing Chen; Yang Zhang; Yu Shen; Liang Jiang; Guangbo Zhang; Xueguang Zhang; Yang Xu; Yang Xu; Fengqing Fu

doi:10.3389/fimmu.2023.1255667

Frontiers in Immunology (Nov 2023)

Deficiency of N-linked glycosylation impairs immune function of B7-H6

Hanqing Chen,
Hanqing Chen,
Yang Zhang,
Yu Shen,
Liang Jiang,
Guangbo Zhang,
Xueguang Zhang,
Yang Xu,
Yang Xu,
Fengqing Fu

Affiliations

Hanqing Chen: Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China
Hanqing Chen: Department of Hematology, the First affiliated Hospital of Soochow University, Suzhou, China
Yang Zhang: Department of Respiratory and Critical Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
Yu Shen: Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China
Liang Jiang: Suzhou Red Cross Blood Center, Suzhou, China
Guangbo Zhang: Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China
Xueguang Zhang: Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China
Yang Xu: Department of Hematology, the First affiliated Hospital of Soochow University, Suzhou, China
Yang Xu: National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China
Fengqing Fu: Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China

DOI: https://doi.org/10.3389/fimmu.2023.1255667
Journal volume & issue: Vol. 14

Abstract

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B7-H6 is a novel immune checkpoint molecule that triggers NK cell cytotoxicity, but the role of N-glycosylation in B7-H6 is poorly understood. We here identified the existence of N-glycosylation of B7-H6 in different cell lines and exogenous expression cells by PNGase F digestion and tunicamycin blockage. Subsequently, we demonstrated that B7-H6 contains 6 functional N-linked glycosylation sites by single site mutation and electrophoresis. Phylogenetical and structural analysis revealed that N43 and N208 glycan are conserved in jawed vertebrates and may thus contribute more to the biological functions. We further demonstrated that N43 and N208 glycosylation are essential for B7-H6 to trigger NK cell activation. Mechanistically, we found that N43 and N208 glycan contributed to the stability and membrane expression of B7-H6 protein. Lack of N208 glycosylation led to membrane B7-H6 shedding, while N43 mutation resulted in impaired B7-H6/NKp30 binding affinity. Together, our findings highlight the significance of N-linked glycosylation in B7-H6 biological functions and suggest potential targets for modulating NK cell-mediated immunity.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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