3RTQ

Structure of the mouse CD1d-HS44-iNKT TCR complex

3RTQ の概要

• エントリーDOI: 10.2210/pdb3rtq/pdb
• 分子名称: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, Valpha14 (mouse variable domain, human constant domain), ... (9 entities in total)
• 機能のキーワード: antigen presentation, glycolipid, nkt cells, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 96572.21

構造登録者

Yu, E.D.,Zajonc, D.M. (登録日: 2011-05-03, 公開日: 2012-02-22, 最終更新日: 2024-10-16)

主引用文献

Kerzerho, J.,Yu, E.D.,Barra, C.M.,Alari-Pahisa, E.,Girardi, E.,Harrak, Y.,Lauzurica, P.,Llebaria, A.,Zajonc, D.M.,Akbari, O.,Castano, A.R.
Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties.
J.Immunol., 188:2254-2265, 2012

PubMed 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.

PubMed: 22301545
DOI: 10.4049/jimmunol.1103049

実験手法

X-RAY DIFFRACTION (2.8 Å)