T Cell Receptor CDR2β and CDR3β Loops Collaborate Functionally to Shape the iNKT Cell Repertoire
T Cell Receptor CDR2β and CDR3β Loops Collaborate Functionally to Shape the iNKT Cell Repertoire
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DOI：
10.1016/j.immuni.2009.05.010
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发表时间：
2009-07-17
期刊：
影响因子：
32.4
通讯作者：
Gapin, Laurent
中科院分区：
文献类型：
--
作者：
Mallevaey, Thierry;Scott-Browne, James P.;Gapin, Laurent
小鼠I型自然杀伤T细胞受体（iNKT TCR）使用单一的Vα14 - Jα18序列以及几乎总是Vβ8.2、Vβ7或Vβ2的Vβ，尽管这种差异使用的基础尚不清楚。我们发现Vβ偏向是由于CDR2β环决定了iNKT TCR对CD1d - 糖脂的亲和力，从而控制了阳性选择。在一个保守的iNKT - TCR - CD1d对接框架内，这些固有的Vβ - CD1d亲和力受到高变的CDR3β环的进一步调节，从而确定了iNKT TCR的两个CDRβ环之间的功能性相互作用。这些Vβ偏向揭示了一种广泛的层级反应，在识别多种CD1d配体时，Vβ8.2 > Vβ7 > Vβ2。在胸腺选择过程中iNKT TCR库的这种限制矛盾地确保了每个外周iNKT细胞识别相似的抗原谱。
Mouse type I natural killer T cell receptors (iNKT TCRs) use a single V alpha 14-J alpha 18 sequence and V beta s that are almost always V beta 8.2, V beta 7, or V beta 2, although the basis of this differential usage is unclear. We showed that the V beta bias occurred as a consequence of the CDR2 beta loops determining the affinity of the iNKT TCR for CD1d-glycolipids, thus controlling positive selection. Within a conserved iNKT-TCR-CD1d docking framework, these inherent V beta-CD1d affinities are further modulated by the hypervariable CDR3 beta loop, thereby defining a functional interplay between the two iNKT TCR CDR beta loops. These V beta biases revealed a broadly hierarchical response in which V beta 8.2>V beta 7>V beta 2 in the recognition of diverse CD1d ligands. This restriction of the iNKT TCR repertoire during thymic selection paradoxically ensures that each peripheral iNKT cell recognizes a similar spectrum of antigens.