The interaction of galectin-8 C-terminal domain with cell surface glycoconjugates modulates membrane elasticity to stimulate antigen uptake and presentation to CD4 T cells.

Autor:	Prato CA; Instituto de Investigaciones Biotecnológicas (IIBIO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín (UNSAM), San Martín, Buenos Aires, Argentina., Borbolla LV; Instituto de Investigaciones Biotecnológicas (IIBIO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín (UNSAM), San Martín, Buenos Aires, Argentina., Lizarraga L; Centro de Investigaciones en Bionanociencias (CIBION), CONICET. Ciudad de Buenos Aires, Argentina., Campetella O; Instituto de Investigaciones Biotecnológicas (IIBIO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín (UNSAM), San Martín, Buenos Aires, Argentina., Tribulatti MV; Instituto de Investigaciones Biotecnológicas (IIBIO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín (UNSAM), San Martín, Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Oct 04. Date of Electronic Publication: 2024 Oct 04.
DOI:	10.1093/jleuko/qiae214
Abstrakt:	Galectins constitute a family of soluble lectins with unique capacity to induce macroscale rearrangements upon interacting with cell membrane glycoconjugates. Galectin-8 (Gal-8) is acknowledged for its role in facilitating antigen uptake and processing upon engaging with cell surface glycoconjugates on antigen-presenting cells (APCs). Gal-8 consists of two covalently fused N- and C-terminal carbohydrate recognition domains (N- and C-CRD), each exhibiting distinct glycan specificity. In this study, we utilized single N- and C-CRD recombinant proteins to dissect the nature of Gal-8-glycan interactions during antigen internalization enhancement. Single C-CRD was able to replicate the effect of full-length Gal-8 (FLGal-8) on antigen internalization in BMDCs. Antigen uptake enhancement was diminished in the presence of lactose or when N-glycosylation-deficient macrophages served as APCs, underscoring the significance of glycan recognition. Measurement of the elastic modulus using Atomic Force Microscopy unveiled that FLGal-8- and C-CRD-stimulated macrophages exhibited heightened membrane stiffness compared to untreated cells, providing a plausible mechanism for their involvement in endocytosis. C-CRD proved to be as efficient as FLGal-8 in promoting antigen degradation, suggesting its implication in antigen-processing induction. Lastly, C-CRD was able to replicate FLGal-8-induced antigen presentation in the MHC-II context both in vitro and in vivo. Our findings support the notion that Gal-8 binds through its C-CRD to cell surface N-glycans, thereby altering membrane mechanical forces conducive to soluble antigen endocytosis, processing, and presentation to cognate CD4 T-cells. These findings contribute to a deeper comprehension of Gal-8 and its mechanisms of action, paving the way for the development of more efficacious immunotherapies. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)
Databáze:	MEDLINE
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