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

• DOI: 10.1093/jleuko/qiae214
• Publication Date: 2024-10-04T14:46:50Z
• Authors: Cecilia A Prato; Laura V Borbolla; Leonardo Lizarraga; Oscar Campetella; María V Tribulatti
• Keywords: Glycoconjugate; Galectin; Galectin-3; Elasticity; Cell membrane

Galectins constitute a family of soluble lectins with unique capacity to induce macroscale rearrangements upon interacting cell membrane glycoconjugates. Galectin-8 (Gal-8) is acknowledged for its role in facilitating antigen uptake and processing engaging surface glycoconjugates on antigen-presenting cells (APCs). Gal-8 consists two covalently fused N- C-terminal carbohydrate recognition domains (N- C-CRD), each exhibiting distinct glycan specificity. In this study, we utilized single C-CRD recombinant proteins dissect the nature Gal-8-glycan interactions during internalization enhancement. Single was able replicate effect full-length (FLGal-8) BMDCs. Antigen enhancement diminished presence lactose or when N-glycosylation-deficient macrophages served as APCs, underscoring significance recognition. Measurement elastic modulus using Atomic Force Microscopy unveiled that FLGal-8- C-CRD-stimulated exhibited heightened stiffness compared untreated cells, providing plausible mechanism their involvement endocytosis. proved be efficient FLGal-8 promoting degradation, suggesting implication antigen-processing induction. Lastly, FLGal-8-induced presentation MHC-II context both vitro vivo. Our findings support notion binds through N-glycans, thereby altering mechanical forces conducive endocytosis, processing, cognate CD4 T-cells. These contribute deeper comprehension mechanisms action, paving way development more efficacious immunotherapies.