The T cell antigen receptor expressed by Valpha14i NKT cells has a unique mode of glycosphingolipid antigen recognition

Natural killer (NK) T cells with an invariant Valpha14 rearrangement (Valpha14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid alpha-galactosyl ceramide (alpha-GalCer) presented by CD1d, and they may have important regulatory f...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (33), p.12254-12259
Main Authors: Sidobre, Stéphane, Hammond, Kirsten J L, 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
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens - chemistry
Antigens - metabolism
Antigens, CD1 - chemistry
Antigens, CD1 - metabolism
Antigens, CD1d
Binding Sites
Cells
Cytokines - biosynthesis
Gene expression
Glycosphingolipids - chemistry
Glycosphingolipids - immunology
Glycosphingolipids - metabolism
In Vitro Techniques
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Kinetics
Lipids
Macromolecular Substances
Mice
Mice, Inbred C57BL
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - metabolism
Solubility
T cell receptors
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
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Summary:Natural killer (NK) T cells with an invariant Valpha14 rearrangement (Valpha14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid alpha-galactosyl ceramide (alpha-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the Valpha14i T cell antigen receptor (TCR) has a high affinity for the alpha-GalCer/CD1d complex, driven by a long half-life (t(1/2)). Although this result could have reflected the unique attributes of alpha-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of Valpha14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t(1/2). Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the Valpha14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by Valpha14i NKT cells.
ISSN:0027-8424
1091-6490