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

doi:10.1073/pnas.0404632101

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

^*Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121; ^†School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; ^‡Department of Chemistry, Unit 3060, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060; ^§Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan; and ^¶Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

Communicated by Howard M. Grey, La Jolla Institute for Allergy and Immunology, San Diego, CA, June 29, 2004 (received for review March 24, 2004)

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 (t _1/2). 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 t _1/2. 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.

Footnotes

↵ ∥ To whom correspondence should be addressed. E-mail: mitch{at}liai.org.
Abbreviations: α-GalCer, α-galactosyl ceramide; α-ManCer, α-mannosyl ceramide; β-Gal-Cer, β-galactosyl ceramide; NK, natural killer; RU, resonance units; sc, single chain; TCR, T cell antigen receptor; Vα14i, invariant Vα14 rearrangement.