A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
AuthorKjer-Nielsen, L; Borg, NA; Pellicci, DG; Beddoe, T; Kostenko, L; Clements, CS; Williamson, NA; Smyth, MJ; Besra, GS; Reid, HH; ...
Source TitleJOURNAL OF EXPERIMENTAL MEDICINE
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sKjer-Nielsen, Lars; Pellicci, Daniel; Kostenko, Lyudmila; Williamson, Nicholas; McCluskey, James; Godfrey, Dale; Bharadwaj, Mandvi
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsKjer-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, A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition, JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (3), pp. 661 - 673
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118261
C1 - Journal Articles Refereed
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.
KeywordsCellular Immunology; Immune System and Allergy
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