A public human population of TRAV26+ type II natural killer T cells recognises CD1d in a lipid-independent manner
Abstract Most studies of CD1d-restricted natural killer T cells (NKT) have focused on type I TRAV10-TRAJ18 + NKT cells that recognise the glycolipid α-GalCer. Our understanding of type II NKT cells, their T cell receptor (TCR) gene usage, and their ligand specificity and diversity remains unclear. Here, using CD1d tetramers carrying diverse endogenous lipids (CD1d-endo), we identified public human TRAV26 + type II NKT TCRs present in all examined individuals, with many expressing a conserved TRAV26-2-TRAJ48 TCRα chain. Cellular, molecular and lipidomic analyses showed that TRAV26 + TCRs bound with similar affinities to CD1d loaded with diverse lipids, suggesting lipid-independent binding. Crystal structures of TRAV26 + TCR-CD1d complexes suggested these TCRs bound solely to the A’-roof of CD1d, distal to the protruding lipid. Collectively, we have uncovered a population of public lipid-independent TRAV26 + type II NKT cells.
Authors
- Catarina F. Almeida (ORCID: https://orcid.org/0000-0002-3393-4411)
- Caroline Soliman (ORCID: https://orcid.org/0000-0003-2714-5341)
- Christopher M. Harpur (ORCID: https://orcid.org/0000-0002-3238-9861)
- Jérôme Le Nours (ORCID: https://orcid.org/0000-0002-2221-7636)
- Tan‐Yun Cheng (ORCID: https://orcid.org/0000-0002-5178-6985)
- Elena Batleska
- Dale Ian Godfrey (ORCID: https://orcid.org/0000-0002-3009-5472)
- Daniel Grant Pellicci (ORCID: https://orcid.org/0000-0001-5305-2398)
- Jamie Rossjohn (ORCID: https://orcid.org/0000-0002-2020-7522)
- Adam P. Uldrich (ORCID: https://orcid.org/0000-0002-6350-5976)
- Catriona Vi Nguyen-Robertson (ORCID: https://orcid.org/0000-0001-8751-4503)
- Kean Chan Yew Poa (ORCID: https://orcid.org/0000-0003-4090-9561)
- Christopher Menne (ORCID: https://orcid.org/0000-0003-2211-8766)
- Geovane Marques-Ferreira
- D. Branch Moody
- Scott JJ Reddiex
- Alison A. White (ORCID: https://orcid.org/0009-0007-4733-7152)
- Rajesh Lamichhane
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-07
- DOI
- https://doi.org/10.1038/s41467-026-78124-5
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00