A molecular basis for NKT cell recognition of CD1d-self-antigen |
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Authors: | Mallevaey Thierry Clarke Andrew J Scott-Browne James P Young Mary H Roisman Laila C Pellicci Daniel G Patel Onisha Vivian Julian P Matsuda Jennifer L McCluskey James Godfrey Dale I Marrack Philippa Rossjohn Jamie Gapin Laurent |
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Institution: | Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA. |
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Abstract: | 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???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. |
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