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.
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BibTeX
@article{poa2026public,
title = {{A public human population of TRAV26+ type II natural killer T cells recognises CD1d in a lipid-independent manner}},
author = {Kean Chan Yew Poa and Christopher M. Harpur and Tan-Yun Cheng and Elena Batleska and Catriona V. Nguyen-Robertson and Rajesh Lamichhane and Alison A. White and Geovane Marques-Ferreira and Caroline Soliman and Scott JJ Reddiex and Christopher Menne and Adam P. Uldrich and D. Branch Moody and Jamie Rossjohn and Dale I. Godfrey and Daniel G. Pellicci and Jérôme Le Nours and Catarina F. Almeida},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78124-5},
url = {https://www.nature.com/articles/s41467-026-78124-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A public human population of TRAV26+ type II natural killer T cells recognises CD1d in a lipid-independent manner
AU - Kean Chan Yew Poa
AU - Christopher M. Harpur
AU - Tan-Yun Cheng
AU - Elena Batleska
AU - Catriona V. Nguyen-Robertson
AU - Rajesh Lamichhane
AU - Alison A. White
AU - Geovane Marques-Ferreira
AU - Caroline Soliman
AU - Scott JJ Reddiex
AU - Christopher Menne
AU - Adam P. Uldrich
AU - D. Branch Moody
AU - Jamie Rossjohn
AU - Dale I. Godfrey
AU - Daniel G. Pellicci
AU - Jérôme Le Nours
AU - Catarina F. Almeida
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78124-5
UR - https://www.nature.com/articles/s41467-026-78124-5
AB - 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.
SN - 2041-1723
ER -