5VCJ
Structure of alpha-galactosylphytosphingosine bound by CD1d and in complex with the Va14Vb8.2 TCR
Summary for 5VCJ
| Entry DOI | 10.2210/pdb5vcj/pdb |
| Descriptor | Antigen-presenting glycoprotein CD1d1, Beta-2-microglobulin, Chimeric TCR Valpha14/Jalpha18 chain (mouse variable domain, human constant domain), ... (8 entities in total) |
| Functional Keywords | immune system, antigen-presentation, tcr, mhc-fold |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 4 |
| Total formula weight | 96611.09 |
| Authors | Wang, J.,Zajonc, D.M. (deposition date: 2017-03-31, release date: 2018-04-04, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 30656346DOI: 10.1039/c8ob02982b PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.16 Å) |
Structure validation
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