2eyr

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

File:2eyr.gif


2eyr, resolution 2.40Å

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OverviewOverview

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.

About this StructureAbout this Structure

2EYR is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition., Kjer-Nielsen L, Borg NA, Pellicci DG, Beddoe T, Kostenko L, Clements CS, Williamson NA, Smyth MJ, Besra GS, Reid HH, Bharadwaj M, Godfrey DI, Rossjohn J, McCluskey J, J Exp Med. 2006 Mar 20;203(3):661-73. Epub 2006 Feb 27. PMID:16505140

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