N-linked glycans: an underappreciated key determinant of T cell development, activation, and function

Abdelbary, Mahmoud; Nolz, Jeffrey C.

doi:10.1097/in9.0000000000000035

Cited by 2 publications

(2 citation statements)

References 123 publications

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“…The oligosaccharide constituents of proteins are used by viruses and bacteria to interact with a host immune system [ 11 , 15 , 16 ]. First, we investigated whether the SARS-CoV-2 S protein, which does indeed contain glycan moieties [ 12 , 13 ], was able to bind to the Con A, a lectin capable of binding glycan (preferably mannan) moieties [ 17 ] and known to be a potent lymphocyte mitogen [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Considering the number and complexity of receptor/ligand systems whose interactions depend on the glycan moieties and their relevance in anti-pathogen immunity [ 11 , 15 , 16 ], the biological significance of glycan moieties decorating the S protein of SARS-CoV-2 is an attractive topic for research aimed at ascertaining the role of N-glycans in protection from, and/or pathology of, COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects

Barbati,

Bromuro,

Vendetti

et al. 2024

Viruses

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The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-COVID-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up-modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans, as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of the mannose receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of COVID-19 pathology and immunity to SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects

Barbati,

Bromuro,

Vendetti

et al. 2024

Viruses

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A proton channel, Otopetrin 1 (OTOP1) is N‐glycosylated at two asparagine residues in third extracellular loop

Sasaki,

Yano‐Nashimoto,

Yamaguchi

2024

Journal Cellular Physiology

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A proton (H+) channel, Otopetrin 1 (OTOP1) is an acid sensor in the sour taste receptor cells. Although OTOP1 is known to be activated by extracellular acid, no posttranslational modification of OTOP1 has been reported. As one of the posttranslational modifications, glycosylation is known to modulate many ion channels. In this study, we investigated whether OTOP1 is glycosylated and how the glycosylation affects OTOP1 function. Pharmacological and enzymatic examinations (using an N‐glycosylation inhibitor, tunicamycin and peptide: N‐glycanase F [PNGase F]) revealed that overexpressed mouse OTOP1 was N‐glycosylated. As the N‐glycans were Endoglycosidase H (Endo H)‐sensitive, they were most likely high‐mannose type. A site‐directed mutagenesis approach revealed that both two asparagine residues (N238 and N251) in the third extracellular loop between the fifth transmembrane region and the sixth transmembrane region (L5‐6) were the glycosylation sites. Prevention of the glycosylations by the mutations of the asparagine residues or by tunicamycin treatment diminished the whole‐cell OTOP1 current densities. The results of cell surface biotinylation assay showed that the prevention of the glycosylations reduced the surface expression of OTOP1 at the plasma membrane. These results indicate that mouse OTOP1 is N‐glycosylated at N238 and N251, and that the glycosylations are necessary for OTOP1 to show the maximum degree of H+ current densities at the plasma membrane through promoting its targeting to the plasma membrane. These findings on glycosylations of OTOP1 will be a part of a comprehensive understanding on the regulations of OTOP1 function.

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N-linked glycans: an underappreciated key determinant of T cell development, activation, and function

Cited by 2 publications

References 123 publications

The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects

The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects

A proton channel, Otopetrin 1 (OTOP1) is N‐glycosylated at two asparagine residues in third extracellular loop

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