PDBsum entry 4en3

Immune system

PDB id: 4en3

Contents

Protein chains

257 a.a.

186 a.a.

240 a.a.

99 a.a.

Ligands

NAG ×5

AGH

FUC

GOL ×2

Waters ×109

PDB id:

4en3

Name:

Immune system

Title:

Crystal structure of a human valpha24(-) nkt tcr in complex with cd1d/alpha-galactosylceramide

Structure:

Antigen-presenting glycoprotein cd1d. Chain: c. Fragment: unp residues 21-295. Synonym: r3g1. Engineered: yes. Human nkt tcr alpha chain. Chain: a. Engineered: yes. Human nkt tcr beta chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd1d. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: b2m, cdabp0092, hdcma22p.

Resolution:

2.57Å R-factor: 0.211 R-free: 0.266

Authors:

J.Lopez-Sagaseta,E.J.Adams

Key ref:

J.López-Sagaseta et al. (2012). The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor. Plos Biol, 10, e1001412. PubMed id: 23109910

Date:

12-Apr-12 Release date: 31-Oct-12

Protein chain

P15813  (CD1D_HUMAN) -  Antigen-presenting glycoprotein CD1d from Homo sapiens

Seq: 335 a.a.

Struc: 257 a.a.

Protein chain

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

Seq: 220 a.a.

Struc: 186 a.a.

Protein chain

K7N5M4  (K7N5M4_HUMAN) -  Human nkt tcr beta chain from Homo sapiens

Seq: 259 a.a.

Struc: 240 a.a.

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

Plos Biol 10:e1001412 (2012)

PubMed id: 23109910

The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.

J.López-Sagaseta, J.E.Kung, P.B.Savage, J.Gumperz, E.J.Adams.

ABSTRACT

CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases. Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT cells, which comprise a subset of the human CD1d-restricted T cell population. In contrast, little is known about how lipid antigens are recognized by functionally distinct CD1d-restricted T cells bearing different TCRα chain rearrangements. Here we present crystallographic and biophysical analyses of α-galactosylceramide (α-GalCer) recognition by a human CD1d-restricted TCR that utilizes a Vα3.1-Jα18 rearrangement and displays a more restricted specificity for α-linked glycolipids than that of iNKT TCRs. Despite having sequence divergence in the CDR1α and CDR2α loops, this TCR employs a convergent recognition strategy to engage CD1d/αGalCer, with a binding affinity (∼2 µM) almost identical to that of an iNKT TCR used in this study. The CDR3α loop, similar in sequence to iNKT-TCRs, engages CD1d/αGalCer in a similar position as that seen with iNKT-TCRs, however fewer actual contacts are made. Instead, the CDR1α loop contributes important contacts to CD1d/αGalCer, with an emphasis on the 4'OH of the galactose headgroup. This is consistent with the inability of Vα24- T cells to respond to α-glucosylceramide, which differs from αGalCer in the position of the 4'OH. These data illustrate how fine specificity for a lipid containing α-linked galactose is achieved by a TCR structurally distinct from that of iNKT cells.