4EN3

Crystal structure of a human Valpha24(-) NKT TCR in complex with CD1d/alpha-galactosylceramide

Summary for 4EN3

• Entry DOI: 10.2210/pdb4en3/pdb
• Descriptor: Antigen-presenting glycoprotein CD1d, HUMAN NKT TCR ALPHA CHAIN, HUMAN NKT TCR BETA CHAIN, ... (9 entities in total)
• Functional Keywords: immunoglobulin-like, mhc class i-like, antigen presentation-recognition, membrane, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 100360.87

Authors

Lopez-Sagaseta, J.,Adams, E.J. (deposition date: 2012-04-12, release date: 2012-10-31, Last modification date: 2024-10-30)

Primary citation

Lopez-Sagaseta, J.,Kung, J.E.,Savage, P.B.,Gumperz, J.,Adams, E.J.
The Molecular Basis for Recognition of CD1d/alpha-Galactosylceramide by a Human Non-Valpha24 T Cell Receptor Struct. Title
Plos Biol., 10:e1001412-e1001412, 2012

PubMed 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.

PubMed: 23109910
DOI: 10.1371/journal.pbio.1001412

Experimental method

X-RAY DIFFRACTION (2.568 Å)