PDBsum entry 4zak

Immune system

PDB id: 4zak

Contents

Protein chains

267 a.a.

98 a.a.

203 a.a.

239 a.a.

Ligands

NAG-NAG

NAG ×2

4LX

PDB id:

4zak

Name:

Immune system

Title:

Crystal structure of the mcd1d/db06-1/inktcr ternary complex

Structure:

Antigen-presenting glycoprotein cd1d1. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Protein trav11,va14ja18/vb8.2,human nkt tcr alpha chain. Chain: c. Synonym: protein trav11d,human nkt tcr beta chain.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cd1d1, cd1.1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: b2m. Mus musculus, homo sapiens. Mouse, human.

Resolution:

2.82Å R-factor: 0.218 R-free: 0.256

Authors:

D.M.Zajonc,A.M.Birkholz

Key ref:

A.M.Birkholz et al. (2015). A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-γ Production. J Immunol, 195, 924-933. PubMed id: 26078271 DOI: 10.4049/jimmunol.1500070

Date:

13-Apr-15 Release date: 01-Jul-15

Protein chain

P11609  (CD1D1_MOUSE) -  Antigen-presenting glycoprotein CD1d1 from Mus musculus

Seq: 336 a.a.

Struc: 267 a.a.

Protein chain

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 98 a.a.

Protein chain

A0A0B4J1J9  (A0A0B4J1J9_MOUSE) -  T cell receptor alpha variable 11 (Fragment) from Mus musculus

Seq: 114 a.a.

Struc: 203 a.a.

Protein chain

A0A0G2JG46  (A0A0G2JG46_MOUSE) -  T cell receptor alpha joining 18 (Fragment) from Mus musculus

Seq: 22 a.a.

Struc: 203 a.a.*

Protein chain

K7N5M3  (K7N5M3_HUMAN) -  Human nkt tcr alpha chain from Homo sapiens

Seq: 220 a.a.

Struc: 203 a.a.*

Protein chain

A0A5B9  (TRBC2_HUMAN) -  T cell receptor beta constant 2 from Homo sapiens

Seq: 178 a.a.

Struc: 239 a.a.*

Protein chain

A0N8J3  (A0N8J3_MOUSE) -  Tcell receptor chain (Fragment) from Mus musculus

Seq: 281 a.a.

Struc: 239 a.a.*

Protein chain

A2NTY6  (A2NTY6_MOUSE) -  Beta-chain (Fragment) from Mus musculus

Seq: 144 a.a.

Struc: 239 a.a.*

* PDB and UniProt seqs differ at 172 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1500070

J Immunol 195:924-933 (2015)

PubMed id: 26078271

A Novel Glycolipid Antigen for NKT Cells That Preferentially Induces IFN-γ Production.

A.M.Birkholz, E.Girardi, G.Wingender, A.Khurana, J.Wang, M.Zhao, S.Zahner, P.A.Illarionov, X.Wen, M.Li, W.Yuan, S.A.Porcelli, G.S.Besra, D.M.Zajonc, M.Kronenberg.

ABSTRACT

In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with the only change being a single atom: the substitution of a carbonyl oxygen with a sulfur atom. Although DB06-1 is not a more effective Ag in vitro, the small chemical change has a marked impact on the ability of this lipid Ag to stimulate iNKT cells in vivo, with increased IFN-γ production at 24 h compared with αGalCer, increased IL-12, and increased activation of NK cells to produce IFN-γ. These changes are correlated with an enhanced ability of DB06-1 to load in the CD1d molecules expressed by dendritic cells in vivo. Moreover, structural studies suggest a tighter fit into the CD1d binding groove by DB06-1 compared with αGalCer. Surprisingly, when iNKT cells previously exposed to DB06-1 are restimulated weeks later, they have greatly increased IL-10 production. Therefore, our data are consistent with a model whereby augmented and or prolonged presentation of a glycolipid Ag leads to increased activation of NK cells and a Th1-skewed immune response, which may result, in part, from enhanced loading into CD1d. Furthermore, our data suggest that strong antigenic stimulation in vivo may lead to the expansion of IL-10-producing iNKT cells, which could counteract the benefits of increased early IFN-γ production.