Abstract
Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d–α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1+ type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7–8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A′-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d–α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.
Highlights
Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex
The human type I NKT cell repertoire is comprised of the invariant TRAV10 þ TRAJ18 þ TRBV25-1 þ NKT cells
We detected a clear population of TRBV25-1 À NKT cells, that, in most donors, did not react with ‘endogenous’ CD1d tetramers, implying these cells recognized a-GalCer presented by CD1d (Fig. 1a)
Summary
Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. We describe an atypical population of CD1d–a-galactosylceramide (a-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1 þ type I NKT cell repertoire. These cells express a range of TCR a- and b-chains that show differential recognition of glycolipid antigens. Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. We describe a diverse population of CD1d–a-GalCer reactive cells that we termed ‘atypical NKT cells’ because they lack the invariant TRAV10 þ TRAJ18 þ a-chain and the TRBV25-1 b-chain that are inherent to type I NKT cells. Variations in the CD1d–a-GalCer-reactive NKT TCR repertoire can manifest in alternative docking strategies on CD1d and diverse reactivity towards CD1d-restricted lipids
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