Public and private T cell receptor repertoires define NKT cell subsets with reactivity to CD1d-α-GalCer (#154)
Human type 1 NKT cells are a unique subset of T lymphocytes that utilize a Vα24Jα18+ Vβ11+ semi-invariant T cell receptor, which confers reactivity to CD1d-α-galactosylceramide (α-GalCer). Despite their potential biological importance, the diversity of the NKT cell TCR repertoire remains poorly defined. By enriching for CD1d-α-GalCer-reactive NKT cells derived from healthy human blood samples, we have identified rare yet diverse subsets of αβTCR+ NKT cells that utilized ‘private’ TCR repertoires consisting of atypical Vα24- Jα18- Vβ11- TCR gene rearrangements, which appeared to supplement the canonical ‘public’ TCR repertoires. Additionally, we also identified unusual Vδ1+ αβTCR+ (termed ‘δ/αβ’ cells) and γδTCR+ subsets that reacted with CD1d-α-GalCer. These TCRs each conferred an altered hierarchy of glycolipid Ag recognition and unique mode of CD1d binding compared to type 1 NKT cells. Accordingly, diverse NKT cell TCR repertoire usage potentially provides far greater scope for glycolipid Ag recognition than what is currently appreciated.