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Publication : Mechanisms imposing the Vbeta bias of Valpha14 natural killer T cells and consequences for microbial glycolipid recognition.

First Author  Wei DG Year  2006
Journal  J Exp Med Volume  203
Issue  5 Pages  1197-207
PubMed ID  16651387 Mgi Jnum  J:124137
Mgi Id  MGI:3720560 Doi  10.1084/jem.20060418
Citation  Wei DG, et al. (2006) Mechanisms imposing the Vbeta bias of Valpha14 natural killer T cells and consequences for microbial glycolipid recognition. J Exp Med 203(5):1197-207
abstractText  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 Valpha14-Jalpha18 TCR alpha chain for antigen recognition by NKT cells is well recognized, but the mechanisms underlying the Vbeta8, Vbeta7, and Vbeta2 bias in mouse have not been explored. To study the influences of thymic selection and the constraints of pairing with Valpha14-Jalpha18, we have created a population of mature T cells expressing Valpha14-Jalpha18 TCR alpha chain in CD1d-deficient mice and studied its recognition properties in vitro and in vivo. Transgenic cells expressed a diverse Vbeta repertoire but their recognition of endogenous ligands and synthetic iGb3 was restricted to the same biased Vbeta 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 Vbeta chains, including the biased NKT set but also Vbeta6, Vbeta9, Vbeta10, and Vbeta14. These surprising findings demonstrate that, whereas Vbeta8, Vbeta7, and Vbeta2 represent the optimal solution for recognition of endogenous ligand, many Vbeta chains that are potentially useful for the recognition of foreign lipids fail to be selected in the NKT cell repertoire.
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