Differential Recognition of CD1d-α-Galactosyl Ceramide by the Vβ8.2 and Vβ7 Semi-invariant NKT T Cell Receptors

Daniel G Pellicci, Onisha Patel, Lars Kjer-Nielsen, Siew Siew Pang, Lucy C Sullivan, Konstantinos Kyparissoudis, Andrew G Brooks, Hugh Harrington Reid, Stephanie Gras, Isabelle S Lucet, Ruide Koh, Mark J Smyth, Thierry Mallevaey, Jennifer L Matsuda, Laurent Gapin, James McCluskey, Dale I Godfrey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

181 Citations (Scopus)


The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid antigens. Although the TCR alpha chain is typically invariant, the beta chain expression is more diverse, where three V beta chains are commonly expressed in mice. We report the structures of V alpha 14-V beta 8.2 and V alpha 14-V beta 7 NKT TCRs in complex with CD1d-alpha-galactosylceramide (alpha-GalCer) and the 2.5 A structure of the human NKT TCR-CD1d-alpha-GalCer complex. Both V beta 8.2 and V beta 7 NKT TCRs and the human NKT TCR ligated CD1d-alpha-GalCer in a similar manner, highlighting the evolutionarily conserved interaction. However, differences within the V beta domains of the V beta 8.2 and V beta 7 NKT TCR-CD1d complexes resulted in altered TCR beta-CD1d-mediated contacts and modulated recognition mediated by the invariant alpha chain. Mutagenesis studies revealed the differing contributions of V beta 8.2 and V beta 7 residues within the CDR2 beta loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V beta usage in NKT cells.
Original languageEnglish
Pages (from-to)47-59
Number of pages13
Issue number1
Publication statusPublished - 2009

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