The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition

Stéphane Sidobre, Kirsten J.L. Hammond, Lise Bénazet-Sidobre, Sergei D. Maltsev, Stewart K. Richardson, Rachel M. Ndonye, Amy R. Howell, Teruyuki Sakai, Gurdyal S. Besra, Steven A. Porcelli, Mitchell Kronenberg

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Natural killer (NK) T cells with an invariant Vα14 rearrangement (Vα14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid α-galactosyl ceramide (α-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Vα14i T cell antigen receptor (TCR) has a high affinity for the α-GalCer/CD1d complex, driven by a long half-life (t1/2). Although this result could have reflected the unique attributes of α-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Vα14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Vα14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Vα14i NKT cells.

Original languageEnglish (US)
Pages (from-to)12254-12259
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number33
DOIs
StatePublished - Aug 17 2004

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    Sidobre, S., Hammond, K. J. L., Bénazet-Sidobre, L., Maltsev, S. D., Richardson, S. K., Ndonye, R. M., Howell, A. R., Sakai, T., Besra, G. S., Porcelli, S. A., & Kronenberg, M. (2004). The T cell antigen receptor expressed by Vα14i NKT cells has a unique mode of glycosphingolipid antigen recognition. Proceedings of the National Academy of Sciences of the United States of America, 101(33), 12254-12259. https://doi.org/10.1073/pnas.0404632101