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Anti-HS44 T cell receptor (Vα14Vβ8.2), pCDTCR1 (TCR-YC0527)

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

HS44, a synthetic aminocyclitolic ceramide analog designed to avoid unrestrained iNKT cell activation. HS44 is a weaker agonist compared to α-GalCer in vitro, while 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 both 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 to 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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Details

  • Target
  • HS44
  • Epitope
  • HS44
  • Format
  • Non-Modified TCR
  • Allele
  • mouse CD1d
  • Vector Name
  • pCDTCR1
  • Vector Length
  • ~ 8 kb
  • Vector Type
  • Lentiviral vector
  • TCR Clone
  • Vα14Vβ8.2
  • Host Species
  • Mouse

Target

  • Introduction
  • Natural killer T cells (NKT cells), unlike conventional T cells, specifically recognize self lipid– or foreign lipid–based antigens bound to the monomorphic MHC class I–like molecule CD1d. NKT cells have been linked to microbial immunity, autoimmunity, allergy and cancer and, accordingly, they represent an important immunotherapeutic target with immense clinical potential. Type I NKT cells express a semi-invariant TCR that has an invariant α-chain and a restricted TCRβ repertoire (α-chain variable region 24–α-chain joining region 18 paired with β-chain variable region 11 (Vα24-Jα18-Vβ11) in humans, and Vα14-Jα18 paired with Vβ8, Vβ7 or Vβ2 in mice). Nevertheless, despite this restricted TCR repertoire, NKT cell TCRs bind an array of different CD1d-restricted lipid-based antigens, including phospholipids9, as well as α-linked and β-linked glycolipids. The α-glycosidic linkage that defines α-galactosylceramide (α-GalCer) and other bacteria-derived NKT cell agonists, including α-glycuronosylceramides and α-galactosyldiacylglycerols, is considered to represent a 'microbial signature', as glycolipid antigens in mammals are typically β-linked anomers. The structures of NKT cell TCRs in complex with many α-linked glycolipids have been determined, including CD1d–α-GalCer and variants thereof and α-galactosyldiacylglycerol. Although the NKT cell TCR has been shown to be relatively rigid, conformational adjustments in complexes of CD1d and α-linked antigen permit optimal engagement of NKT cell TCRs. That is, a conserved docking topology is observed whereby the NKT cell TCR shows a parallel docking mode above the F′ pocket of the CD1d antigen-binding cleft, whereas the α-linked glycosyl moiety 'sits' snug and flat against CD1d, making many direct specificity-governing contacts with the NKT cell TCR.

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For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.

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