Public and private T cell receptor repertoires define NKT cell subsets with reactivity to CD1d-α-GalCer — ASN Events

Public and private T cell receptor repertoires define NKT cell subsets with reactivity to CD1d-α-GalCer (#154)

JEROME LE NOURS 1 , Praveena Thirunavukkarasu 1 , Daniel Pellicci 2 , Nicholas Gherardin 2 , Fiona Ross 2 , Sidonia Eckle 2 , Ricky Lim 2 , Gurdyal Besra 3 , Amy Howell 4 , James McCluskey 2 , Stephanie Gras 1 , Dale Godfrey 2 , Jamie Rossjohn 1 , Adam Uldrich 2
  1. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia
  2. Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia
  3. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK
  4. Department of Chemistry, University of Connecticut, Storrs, CT, USA

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.