Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3382K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kjer-Nielsen, L. Articles by McCluskey, J. Search for Related Content PubMed PubMed Citation Articles by Kjer-Nielsen, L. Articles by McCluskey, J. Pubmed/NCBI databases Protein Structure Substance via MeSH Social Bookmarking                      What's this?

¹ Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
² The Protein Crystallography Unit, ARC Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia
³ Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria 3002, Australia
⁴ School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England, UK

CORRESPONDENCE James McCluskey: jamesm1{at}unimelb.edu.au OR Jamie Rossjohn: Jamie.Rossjohn{at}med.monash.edu.au

Little is known regarding the basis for selection of the semi-invariant ß 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 CDR3ß composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR - and semi-invariant ß-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 CDR3ß 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 CDR3 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 ß TCR and the unique antigen specificity of NKT cells.

Abbreviations used: -GalCer, -galactosylceramide; Ag, antigen; BSA, buried surface area; C, constant; CDR, complementarity-determining region; hCD1d, human CD1d; mCD1d, mouse CD1d; RMS, root mean square; SPR, surface plasmon resonance; V, variable.

L. Kjer-Nielsen and N.A. Borg contributed equally to this work.

J. McCluskey and J. Rossjohn contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Silk, J. D., Salio, M., Reddy, B. G., Shepherd, D., Gileadi, U., Brown, J., Masri, S. H., Polzella, P., Ritter, G., Besra, G. S., Jones, E. Y., Schmidt, R. R., Cerundolo, V. (2008). Cutting Edge: Nonglycosidic CD1d Lipid Ligands Activate Human and Murine Invariant NKT Cells. J. Immunol. 180: 6452-6456 [Abstract] [Full Text]  
• Wun, K. S., Borg, N. A., Kjer-Nielsen, L., Beddoe, T., Koh, R., Richardson, S. K., Thakur, M., Howell, A. R., Scott-Browne, J. P., Gapin, L., Godfrey, D. I., McCluskey, J., Rossjohn, J. (2008). A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR. JEM 205: 939-949 [Abstract] [Full Text]  
• McCarthy, C., Shepherd, D., Fleire, S., Stronge, V. S., Koch, M., Illarionov, P. A., Bossi, G., Salio, M., Denkberg, G., Reddington, F., Tarlton, A., Reddy, B. G., Schmidt, R. R., Reiter, Y., Griffiths, G. M., van der Merwe, P. A., Besra, G. S., Jones, E. Y., Batista, F. D., Cerundolo, V. (2007). The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation. JEM 204: 1131-1144 [Abstract] [Full Text]  
• Hermans, I. F., Silk, J. D., Gileadi, U., Masri, S. H., Shepherd, D., Farrand, K. J., Salio, M., Cerundolo, V. (2007). Dendritic Cell Function Can Be Modulated through Cooperative Actions of TLR Ligands and Invariant NKT Cells. J. Immunol. 178: 2721-2729 [Abstract] [Full Text]  
• Zajonc, D. M., Ainge, G. D., Painter, G. F., Severn, W. B., Wilson, I. A. (2006). Structural Characterization of Mycobacterial Phosphatidylinositol Mannoside Binding to Mouse CD1d. J. Immunol. 177: 4577-4583 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS