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Immunity. 2011 Mar 25;34(3):315-26. doi: 10.1016/j.immuni.2011.01.013. Epub 2011 Mar 3.

A molecular basis for NKT cell recognition of CD1d-self-antigen.

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1
Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA.

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 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.

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PMID:
21376640
PMCID:
PMC3070541
DOI:
10.1016/j.immuni.2011.01.013
[Indexed for MEDLINE]
Free PMC Article

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