Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206, USA.
Immunity. 2011 Mar 25;34(3):315-26. doi: 10.1016/j.immuni.2011.01.013. Epub 2011 Mar 3.
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.
自然杀伤 T 细胞（NKT TCR）的抗原受体结合 CD1d 限制的微生物和自身脂质抗原，尽管自身 CD1d 识别的分子基础尚不清楚。在这里，我们描述了 NKT TCR 对负载天然自身抗原（Ags）的 CD1d 分子的识别，并报告了一个自身反应性 NKT TCR-磷酸肌醇-CD1d 复合物的 2.3 Å 分辨率结构。NKT TCR 对自身和外来抗原的识别是由对 CD1d 的类似的种系编码识别模式支撑的。然而，NKT TCR 的自身反应性是由非种系编码的 CDR3β 环内的独特序列介导的，该序列编码一个疏水性基序，促进与 CD1d 的自身缔合。因此，NKT 细胞自身反应性可能源于 CD1d 和 NKT TCR 之间相互作用的固有亲和力，导致对广泛的 CD1d 限制的自身抗原的识别。这表明，自身反应性 NKT TCR 可以以类似的方式识别多种自身抗原。
