A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells

Kwok S. Wun, Garth Cameron, Onisha Patel, Siew Siew Pang, Daniel G. Pellicci, Lucy C. Sullivan, Santosh Keshipeddy, Mary H. Young, Adam P. Uldrich, Meena S. Thakur, Stewart K. Richardson, Amy R. Howell, Petr A. Illarionov, Andrew G. Brooks, Gurdyal S. Besra, James McCluskey, Laurent Gapin, Steven A. Porcelli, Dale I. Godfrey, Jamie Rossjohn

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t1/2 life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.

Original languageEnglish (US)
Pages (from-to)327-339
Number of pages13
JournalImmunity
Volume34
Issue number3
DOIs
StatePublished - Mar 25 2011

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Wun, K. S., Cameron, G., Patel, O., Pang, S. S., Pellicci, D. G., Sullivan, L. C., Keshipeddy, S., Young, M. H., Uldrich, A. P., Thakur, M. S., Richardson, S. K., Howell, A. R., Illarionov, P. A., Brooks, A. G., Besra, G. S., McCluskey, J., Gapin, L., Porcelli, S. A., Godfrey, D. I., & Rossjohn, J. (2011). A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells. Immunity, 34(3), 327-339. https://doi.org/10.1016/j.immuni.2011.02.001