ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Beyond α-GalCer: Medicinal Chemistry Insights Driving Structural Evolution of CD1d Ligands.Journal of medicinal chemistry · 2026Review
- Unconventional T cells in anti-cancer immunity.Frontiers in immunology · 2025Review
- Editorial: Cognate recognition, functional properties and immunotherapeutic applications of iNKT cells: leveling the road to the clinic.Frontiers in immunology · 2025Article
- State of play in the molecular presentation and recognition of anti-tumor lipid-based analogues.Frontiers in immunology · 2024Review
- Article
- Review
- The CD1 family: serving lipid antigens to T cells since the Mesozoic era.Immunogenetics · 2016Review
- Non-glycosidic compounds can stimulate both human and mouse iNKT cells.European journal of immunology · 2016Article
- Antigen specificity of invariant natural killer T-cells.Biomedical journal · 2015Review
- Invariant natural killer T-cell neutralization is a possible novel therapy for human eosinophilic esophagitis.Clinical & translational immunology · 2014Article
- Stimulation of natural killer T cells by glycolipids.Molecules (Basel, Switzerland) · 2013Review
- Recognition of CD1d-restricted antigens by natural killer T cells.Nature reviews. Immunology · 2012Review
- Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex.The Journal of biological chemistry · 2012Article
- Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells.Immunological reviews · 2012Review
- Turned on by danger: activation of CD1d-restricted invariant natural killer T cells.Immunology · 2012Review
- Natural killer T cell based Immunotherapy.Journal of vaccines & vaccination · 2012Article
- Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation.Journal of nephropathology · 2012Review
- Invariant NKT cells: regulation and function during viral infection.PLoS pathogens · 2012Review
Corrections and comments
- Erratum issuedAlari-Pahisa, Elisenda [corrected to Alari-Pahissa, Elisenda]
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Activation of type I NKT (iNKT) cells by CD1d-presented agonists is a potent immunotherapeutic tool. α-Galactosylceramide (α-GalCer) is the prototypic agonist, but its excessive potency with simultaneous production of both pro- and anti-inflammatory cytokines hampers its potential therapeutic use. In search for novel agonists, we have analyzed the structure and function of HS44, a synthetic aminocyclitolic ceramide analog designed to avoid unrestrained iNKT cell activation. HS44 is a weaker agonist compared with α-GalCer in vitro, although in vivo it induces robust IFN-γ production, and highly reduced but still functional Th2 response. The characteristic cytokine storm produced upon α-GalCer activation was not induced. Consequently, HS44 induced a very efficient iNKT cell-dependent antitumoral response in B16 animal model. In addition, intranasal administration showed the capacity to induce lung inflammation and airway hyperreactivity, a cardinal asthma feature. Thus, HS44 is able to elicit functional Th1 or Th2 responses. Structural studies show that HS44 binds to CD1d with the same conformation as α-GalCer. The TCR binds to HS44 similarly as α-GalCer, but forms less contacts, thus explaining its weaker TCR affinity and, consequently, its weaker recognition by iNKT cells. The ability of this compound to activate an efficient, but not massive, tailored functional immune response makes it an attractive reagent for immune manipulation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.