2EYR

A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition

Summary for 2EYR

• Entry DOI: 10.2210/pdb2eyr/pdb
• Related: 2EYS 2EYT
• Descriptor: NKT12 (3 entities in total)
• Functional Keywords: natural killer t cell receptor, nkt cell receptor, nkt12, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 50857.33

Authors

Kjer-Nielsen, L.,Borg, N.A. (deposition date: 2005-11-09, release date: 2006-03-21, Last modification date: 2023-10-25)

Primary citation

Kjer-Nielsen, L.,Borg, N.A.,Pellicci, D.G.,Beddoe, T.,Kostenko, L.,Clements, C.S.,Williamson, N.A.,Smyth, M.J.,Besra, G.S.,Reid, H.H.,Bharadwaj, M.,Godfrey, D.I.,Rossjohn, J.,McCluskey, J.
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
J.Exp.Med., 203:661-673, 2006

PubMed Abstract: Little is known regarding the basis for selection of the semi-invariant alphabeta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR alpha- and semi-invariant beta-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant alphabeta TCR and the unique antigen specificity of NKT cells.

PubMed: 16505140
DOI: 10.1084/jem.20051777

Experimental method

X-RAY DIFFRACTION (2.4 Å)