Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.

Florence WC, Xia C, Gordy LE, Chen W, Zhang Y, Scott-Browne J, Kinjo Y, Yu KO, Keshipeddy S, Pellicci DG, Patel O, Kjer-Nielsen L, McCluskey J, Godfrey DI, Rossjohn J, Richardson SK, Porcelli SA, Howell AR, Hayakawa K, Gapin L, Zajonc DM, Wang PG, Joyce S
EMBO J. 2009 28 (22): 3579-90

PMID: 19816402 · PMCID: PMC2782097 · DOI:10.1038/emboj.2009.286

The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.

MeSH Terms (17)

Adaptation, Biological Animals Antigen Presentation Antigens, CD1d Antigens, Tumor-Associated, Carbohydrate Cells, Cultured Galactosylceramides Ligands Lymphocyte Activation Mice Mice, Inbred C57BL Models, Molecular Natural Killer T-Cells Receptors, Antigen, T-Cell Receptors, Antigen, T-Cell, alpha-beta Structure-Activity Relationship T-Cell Antigen Receptor Specificity

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