| Literature DB >> 16505140 |
Lars Kjer-Nielsen1, Natalie A Borg, Daniel G Pellicci, Travis Beddoe, Lyudmila Kostenko, Craig S Clements, Nicholas A Williamson, Mark J Smyth, Gurdyal S Besra, Hugh H Reid, Mandvi Bharadwaj, Dale I Godfrey, Jamie Rossjohn, James McCluskey.
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.Entities:
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Year: 2006 PMID： 16505140 PMCID： PMC2118261 DOI： 10.1084/jem.20051777
Source DB: PubMed Journal: J Exp Med ISSN： 0022-1007 Impact factor: 14.307