A molecular basis for NKT cell recognition of CD1d-self-antigen

Thierry Mallevaey, Andrew J Clarke, James P Scott-Browne, Mary H Young, Laila C Roisman, Daniel G Pellicci, Onisha Patel, Julian P Vivian, Jennifer L Matsuda, James McCluskey, Dale I Godfrey, Philippa Marrack, Jamie Rossjohn, Laurent Gapin

Research output: Contribution to journalArticleResearchpeer-review

106 Citations (Scopus)

Abstract

The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 A resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3beta loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.
Original languageEnglish
Pages (from-to)315 - 326
Number of pages12
JournalImmunity
Volume34
Issue number3
DOIs
Publication statusPublished - 2011

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