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The T Cell Antigen Receptor Expressed by Vα14i NKT Cells Has a Unique Mode of Glycosphingolipid Antigen Recognition

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (33), p.12254-12259
Main Authors: Sidobre, Stéphane, Kirsten J. L. Hammond, Bénazet-Sidobre, Lise, Maltsev, Sergei D., Richardson, Stewart K., Ndonye, Rachel M., Howell, Amy R., Sakai, Teruyuki, Besra, Gurdyal S., Porcelli, Steven A., Kronenberg, Mitchell, Grey, Howard M.
Format: Article
Language:English
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0404632101