A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells

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• 作者：Kwok  ; S. Wun¹ ; ⁷ ; Garth Cameron² ; ⁷ ; Onisha Patel¹ ; Siew  ; Siew Pang¹ ; Daniel  ; G. Pellicci² ; Lucy  ; C. Sullivan² ; Santosh Keshipeddy³ ; Mary  ; H. Young⁴ ; Adam  ; P. Uldrich² ; Meena  ; S. Thakur³ ; Stewart  ; K. Richardson³ ; Amy  ; R. Howell³ ; Petr  ; A. Illarionov⁵ ; Andrew  ; G. Brooks² ; Gurdyal  ; S. Besra⁵ ; James McCluskey² ; Laurent Gapin⁴ ; Steven  ; A. Porcelli⁶ ; Dale  ; I. Godfrey² ; ⁸ ; ^{godfrey@unimelb.edu.au} ; Jamie Rossjohn¹ ; ⁸ ; ^{jamie.rossjohn@monash.edu}
• 刊名：Immunity
• 出版年：2011
• 出版时间：25 March 2011
• 年：2011
• 卷：34
• 期：3
• 页码：327-339
• 全文大小：2252 K

文摘

Summary

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.