Antigen specificity of type i NKT cells is governed by TCR beta-chain diversity

Garth Cameron, Daniel G Pellicci, Adam P Uldrich, Gurdyal S Besra, Petr A Illarionov, Spencer John Williams, Nicole L La Gruta, Jamie Rossjohn, Dale I Godfrey

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19 Citations (Scopus)


NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR alpha-chain usage (Valpha14-Jalpha18 in mice, Valpha24-Jalpha18 in humans). However, these cells have diverse TCR beta-chains, including Vbeta8, Vbeta7, and Vbeta2 in mice and Vbeta11 in humans, joined to a range of TCR Dbeta and Jbeta genes. In this study, we demonstrate that TCR beta-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids alpha-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vbeta7+ NKT cells from mice, whereas the alpha-galactosylceramide analog OCH, with a truncated sphingosine chain, was preferentially recognized by Vbeta8+ NKT cells from mice. We show that the influence of the TCR beta-chain is due to a combination of Vbeta-, Jbeta-, and CDR3beta-encoded residues and that these TCRs can recapitulate the selective Ag reactivity in TCR-transduced cell lines. Similar observations were made with human NKT cells where different CDR3beta-encoded residues determined Ag preference. These findings indicate that NKT TCR beta-chain diversity results in differential and nonhierarchical Ag recognition by these cells, which implies that some Ags can preferentially activate type I NKT cell subsets.
Original languageEnglish
Pages (from-to)4604 - 4614
Number of pages11
JournalJournal of Immunology
Issue number10
Publication statusPublished - 2015

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