A Molecular Basis for NKT Cell Recognition of CD1d-Self-Antigen

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• 作者：Thierry Mallevaey¹ ; ⁷ ; ⁹ ; Andrew  ; J. Clarke² ; ⁷ ; James  ; P. Scott-Browne¹ ; ¹⁰ ; Mary  ; H. Young¹ ; Laila  ; C. Roisman² ; Daniel  ; G. Pellicci³ ; Onisha Patel² ; Julian  ; P. Vivian² ; Jennifer  ; L. Matsuda¹ ; James McCluskey³ ; Dale  ; I. Godfrey³ ; Philippa Marrack¹ ; ⁴ ; ⁵ ; ⁶ ; Jamie Rossjohn² ; ⁸ ; ^{jamie.rossjohn@monash.edu} ; Laurent Gapin¹ ; ⁸ ; ^{gapinl@njhealth.org}
• 刊名：Immunity
• 出版年：2011
• 出版时间：25 March 2011
• 年：2011
• 卷：34
• 期：3
• 页码：315-326
• 全文大小：1352 K

文摘

Summary

The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3β loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.