5VCJ

Structure of alpha-galactosylphytosphingosine bound by CD1d and in complex with the Va14Vb8.2 TCR

5VCJ の概要

• エントリーDOI: 10.2210/pdb5vcj/pdb
• 分子名称: Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, Chimeric TCR Valpha14/Jalpha18 chain (mouse variable domain, human constant domain), ... (8 entities in total)
• 機能のキーワード: immune system, antigen-presentation, tcr, mhc-fold
• 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: 96611.09

構造登録者

Wang, J.,Zajonc, D.M. (登録日: 2017-03-31, 公開日: 2018-04-04, 最終更新日: 2024-11-13)

主引用文献

Compton, B.J.,Farrand, K.J.,Tang, C.W.,Osmond, T.L.,Speir, M.,Authier-Hall, A.,Wang, J.,Ferguson, P.M.,Chan, S.T.S.,Anderson, R.J.,Cooney, T.R.,Hayman, C.M.,Williams, G.M.,Brimble, M.A.,Brooks, C.R.,Yong, L.K.,Metelitsa, L.S.,Zajonc, D.M.,Godfrey, D.I.,Gasser, O.,Weinkove, R.,Painter, G.F.,Hermans, I.F.
Enhancing T cell responses and tumour immunity by vaccination with peptides conjugated to a weak NKT cell agonist.
Org. Biomol. Chem., 17:1225-1237, 2019

PubMed Abstract: Activated NKT cells can stimulate antigen-presenting cells leading to enhanced peptide antigen-specific immunity. However, administration of potent NKT cell agonists like α-galactosylceramide (α-GalCer) can be associated with release of high levels of cytokines, and in some situations, hepatotoxicity. Here we show that it is possible to provoke sufficient NKT cell activity to stimulate strong antigen-specific T cell responses without these unwanted effects. This was achieved by chemically conjugating antigenic peptides to α-galactosylphytosphingosine (α-GalPhs), an NKT cell agonist with very weak activity based on structural characterisation and biological assays. Conjugation improved delivery to antigen-presenting cells in vivo, while use of a cathepsin-sensitive linker to release the α-GalPhs and peptide within the same cell promoted strong T cell activation and therapeutic anti-tumour responses in mice. The conjugates activated human NKT cells and enhanced human T cell responses to a viral peptide in vitro. Accordingly, we have demonstrated a means to safely exploit the immunostimulatory properties of NKT cells to enhance T cell activation for virus- and tumour-specific immunity.

PubMed: 30656346
DOI: 10.1039/c8ob02982b

実験手法

X-RAY DIFFRACTION (3.16 Å)