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CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor

机译：半不变的NKT T细胞受体识别CD1d-脂质抗原

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摘要

The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d-antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist α-galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor-peptide-antigen-MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR α-chain and the CD1d-antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR β-chain can impact on recognition of other CD1d-antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.
机译：CD1家族是一大群非多态的主要组织相容性复合物（MHC）-I类分子，它们结合了T细胞识别的不同的基于脂质的抗原。与脂质抗原相互作用的研究最多的T细胞组是自然杀伤性T（NKT）细胞，其特征是表达特异性识别CD1家族成员CD1d的半恒定T细胞受体（NKT TCR）。 NKT细胞介导的对CD1d-抗原复合物的识别与微生物免疫，肿瘤免疫，自身免疫和过敏有关。在这里，我们描述了与CD1d结合的人NKT TCR的结构，该CD1d与有效的NKT细胞激动剂α-半乳糖基神经酰胺，原型CD1d限制性糖脂结合。与T细胞受体-肽-抗原-MHC复合体相反，NKT TCR与CD1d结合裂隙平行并在其最末端对接，从而能够与脂质抗原进行锁钥式相互作用。该结构为高度保守的NKT TCRα链与固有免疫中典型的CD1d-抗原复合物之间的相互作用提供了基础，并且还表明NKT TCRβ链的可变性如何影响其他CD1d-CD-识别抗原复合物。这些发现提供了对T细胞受体如何识别免疫系统的脂质抗原呈递分子的直接见识。

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