The Journal of Experimental Medicine
StemCell Technologies
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Published online 1 May 2006 doi:10.1084/jem.20060418
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 5, 1197-1207
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ARTICLE

 Mechanisms imposing the Vß bias of V{alpha}14 natural killer T cells and consequences for microbial glycolipid recognition

Datsen G. Wei1,3, Shane A. Curran1, Paul B. Savage4, Luc Teyton5, and Albert Bendelac1,2

1 Committee on Immunology and 2 Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637
3 Department of Molecular Biology, Princeton University, Princeton, NJ 08544
4 Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602
5 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE Albert Bendelac: abendela{at}bsd.uchicago.edu

Mouse and human natural killer T (NKT) cells recognize a restricted set of glycosphingolipids presented by CD1d molecules, including self iGb3 and microbial {alpha}-glycuronosylceramides. The importance of the canonical V{alpha}14-J{alpha}18 TCR {alpha} chain for antigen recognition by NKT cells is well recognized, but the mechanisms underlying the Vß8, Vß7, and Vß2 bias in mouse have not been explored. To study the influences of thymic selection and the constraints of pairing with V{alpha}14-J{alpha}18, we have created a population of mature T cells expressing V{alpha}14-J{alpha}18 TCR {alpha} chain in CD1d-deficient mice and studied its recognition properties in vitro and in vivo. Transgenic cells expressed a diverse Vß repertoire but their recognition of endogenous ligands and synthetic iGb3 was restricted to the same biased Vß repertoire as expressed in natural NKT cells. In contrast, {alpha}-GalCer, a synthetic homologue of microbial {alpha}-glycuronosylceramides, was recognized by a broader set of Vß chains, including the biased NKT set but also Vß6, Vß9, Vß10, and Vß14. These surprising findings demonstrate that, whereas Vß8, Vß7, and Vß2 represent the optimal solution for recognition of endogenous ligand, many Vß chains that are potentially useful for the recognition of foreign lipids fail to be selected in the NKT cell repertoire.

Abbreviations used: DN, double negative; DP, double positive; NKT, natural killer T; Tg, transgenic.


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