A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition
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DOI：
10.1084/jem.20051777
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发表时间：
2006-03-20
影响因子：
15.3
通讯作者：
McCluskey, J
中科院分区：
文献类型：
--
作者：
Kjer-Nielsen, L;Borg, NA;McCluskey, J
关于自然杀伤T(NKT)细胞表达的半不变的α-βT细胞受体(TCR)的选择基础或这如何介导CD1d-糖脂复合体的识别，人们知之甚少。我们已经确定了两个人NKT TCR的结构，它们的CDRβ组成和长度不同。这两个TCR在配体界面上都含有一个保守的、带正电的口袋，里面排列着不变的TCR-α和半不变的TCR链的残基。空腔位于中心位置，非常适合与暴露的糖脂抗原的糖基头部基团相互作用。小鼠和人类不变的NKT TCR共同的序列揭示了一个连续的保守的“热点”，为NKT细胞跨物种的反应性提供了基础。结构和功能数据表明，CDR3β环提供了一种可塑性机制，适合识别CD1d提出的各种糖脂抗原。我们提出了一个NKT TCR-CD1d-糖脂相互作用的模型，其中不变的CDR3α环被预测在决定对CD1d的固有偏爱中发挥主要作用。这些发现为选择半不变的α-βTCR和NKT细胞独特的抗原特异性奠定了结构基础。
Little is known regarding the basis for selection of the semi-invariant alpha beta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR-alpha and semi-invariant TCR chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3 beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3 alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi- invariant alpha beta TCR and the unique antigen specificity of NKT cells.