The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells

Shin, Jung Hoon; Park, Seho

doi:10.5483/bmbrep.2014.47.5.077

Cited by 5 publications

(3 citation statements)

References 70 publications

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“…CD1a-c proteins are recognized by diverse conventional αβ T cells, while CD1d proteins are recognized by a specialized subset of αβ T cells. The intracellular metabolic pathways of lipid antigens are key in forming the functional NKT cell repertoire ( 40 , 41 ). We believe that more analysis of the lipid nature of these cells is needed in order to assess their response to the immunomodulatory effect of Biobran/MGN-3.…”

Section: Discussionmentioning

confidence: 99%

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double‑blind, placebo-controlled clinical trial

2018

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Aging is associated with a decline in natural killer (NK) and natural killer T (NKT) cell function that may contribute to increased susceptibility to malignancy and infection. A preliminary investigation was conducted examining the hypothesis that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known immunomodulatory activity, could counteract this decline in NK/NKT cell activity in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56 years old, participated in a randomized, double-blind, placebo-controlled clinical trial. A total of six subjects served as control and six subjects ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3 supplementation on NK/NKT cell activity was assessed using the degranulation assay. All study subjects were monitored for the development of any inadvertent side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood cell components and liver and kidney functions were also assessed. Results demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK cells, however it enhanced the cytotoxic activity of induced NK cell expression of cluster of differentiation 107a, when compared with baseline values and with the placebo group (P<0.05). Furthermore, there were no side effects observed, indicating that Biobran/MGN-3 supplementation was safe at the utilized dosage and for the duration of administration. Various additional beneficial effects were observed, including improved mean corpuscular volume and reduced hepatic aspartate aminotransferase enzyme levels, which suggested improved liver function. It was concluded that Biobran/MGN-3 induces a significant increase in NK activity which may increase resistance to viral infections and cancers in the geriatric population. However, additional clinical trials should be conducted in the future to verify these findings.

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Section: Discussionmentioning

confidence: 99%

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double‑blind, placebo-controlled clinical trial

2018

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“…Although CD1d structurally resembles MHC class I molecules, they are like MHC class II molecules in terms of intracellular trafficking; as such, several studies suggest overall similarities and interdependency in the two antigen presentation pathways. 34,35 Furthermore, we have found that several cell signalling pathways affect both CD1d-and MHC class II-mediated antigen presenta-tion. 23,36 The L-CD1d-DR4 cell line is a murine fibroblast cell line expressing both murine CD1d and the MHC class II molecule, HLA-DR4.…”

Section: Mhc Class Ii-mediated Antigen Presentation Is Not Influencedmentioning

confidence: 99%

STAT3 promotes CD1d‐mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

et al. 2015

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SummaryCytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting cells (APCs) in which STAT3 expression was inhibited exhibited markedly reduced endogenous lipid antigen presentation to NKT cells without an impact on exogenous lipid antigen presentation by CD1d. Consistent with this observation, in APCs where STAT3 was knocked down, dramatically decreased levels of UDP glucose ceramide glucosyltransferase (UGCG), an enzyme involved in the first step of glycosphingolipid biosynthesis, were observed. Impaired lipid antigen presentation was reversed by ectopic expression of UGCG in STAT3-silenced CD1d + APCs. Hence, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d.

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“…Heterodimers of CD1d and β2-microglobulin are assembled in the endoplasmic reticulum (ER) followed by trafficking of CD1d through the secretory pathway to the plasma membrane, where bound lipids are presented to NKT cells ( 6 , 7 ). In addition, through a tyrosine-based sorting motif in its cytoplasmic tail, CD1d is recruited to the endolysosomal system, where bounds lipids are exchanged against other endogenous and exogenous lipids, followed by return of CD1d to the cell surface and presentation of associated lipids ( 7 , 8 ). As such, CD1d broadly surveys different cellular compartments for self- and non-self-derived lipids.…”

Section: Introductionmentioning

confidence: 99%

Sortase A-Cleavable CD1d Identifies Sphingomyelins as Major Class of CD1d-Associated Lipids

et al. 2022

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CD1d is an atypical MHC class I molecule which binds endogenous and exogenous lipids and can activate natural killer T (NKT) cells through the presentation of lipid antigens. CD1d surveys different cellular compartments including the secretory and the endolysosomal pathway and broadly binds lipids through its two hydrophobic pockets. Purification of the transmembrane protein CD1d for the analysis of bound lipids is technically challenging as the use of detergents releases CD1d-bound lipids. To address these challenges, we have developed a novel approach based on Sortase A-dependent enzymatic release of CD1d at the cell surface of live mammalian cells, which allows for single step release and affinity tagging of CD1d for shotgun lipidomics. Using this system, we demonstrate that CD1d carrying the Sortase A recognition motif shows unimpaired subcellular trafficking through the secretory and endolysosomal pathway and is able to load lipids in these compartments and present them to NKT cells. Comprehensive shotgun lipidomics demonstrated that the spectrum and abundance of CD1d-associated lipids is not representative of the total cellular lipidome but rather characterized by preferential binding to long chain sphingolipids and glycerophospholipids. As such, sphingomyelin species recently identified as critical negative regulators of NKT cell activation, represented the vast majority of endogenous CD1d-associated lipids. Moreover, we observed that inhibition of endolysosomal trafficking of CD1d surprisingly did not affect the spectrum of CD1d-bound lipids, suggesting that the majority of endogenous CD1d-associated lipids load onto CD1d in the secretory rather than the endolysosomal pathway. In conclusion, we present a novel system for the analysis of CD1d-bound lipids in mammalian cells and provide new insight into the spectrum of CD1d-associated lipids, with important functional implications for NKT cell activation.

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The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells

Cited by 5 publications

References 70 publications

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double‑blind, placebo-controlled clinical trial

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double‑blind, placebo-controlled clinical trial

STAT3 promotes CD1d‐mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

Sortase A-Cleavable CD1d Identifies Sphingomyelins as Major Class of CD1d-Associated Lipids

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