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A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.

Wun KS, Cameron G, Patel O, Pang SS, Pellicci DG, Sullivan LC, Keshipeddy S, Young MH, Uldrich AP, Thakur MS, Richardson SK, Howell AR, Illarionov PA, Brooks AG, Besra GS, McCluskey J, Gapin L, Porcelli SA, Godfrey DI, Rossjohn J
Immunity 34 327-39 (2011)
Related entries: 3arb, 3are, 3arf, 3arg

Cited: 100 times
EuropePMC logo PMID: 21376639

Abstract

Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t(1/2) life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.

Reviews - 3ard mentioned but not cited (1)

  1. Recognition of CD1d-restricted antigens by natural killer T cells. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. Nat Rev Immunol 12 845-857 (2012)

Articles - 3ard mentioned but not cited (2)



Reviews citing this publication (30)

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Articles citing this publication (67)



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