Distinct CDR3 Conformations in TCRs Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation
Distinct CDR3 Conformations in TCRs Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation
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DOI：
10.4049/jimmunol.181.9.6255
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发表时间：
2008-11-01
影响因子：
4.4
通讯作者：
Kranz, David M.
中科院分区：
文献类型：
--
作者：
Jones, Lindsay L.;Colf, Leremy A.;Kranz, David M.
已知T细胞通过其α β TCR与不同的肽MHC Ag交叉反应。为了探索这种交叉反应性的基础，我们检测了识别两种结构上不同的配体SIY-K-B b和同种异体抗原QL 9-L-d的2C TCR。在这项研究中，我们表征了仅在CDR 3 α环中含有突变的几种高亲和力2C TCR变体的交叉反应性。两个TCR失去了与相互配体（SIY-K-B）交叉反应的能力，而另一个TCR（m67）保持与两种配体的反应性。与QL 9-L-d复合的四种TCR的晶体结构显示，CDR 1、CDR 2和CDR 3 β构象和对接取向非常相似。尽管TCR m67的CDR 3 α环赋予SIY-K-B 2000倍更高的亲和力，但TCR在QL 9-L-d上保持与2C TCR相同的对接角。因此，CDR 3a决定了亲和力和交叉反应性水平，但它这样做并不影响保守的对接方向。免疫学杂志，2008，181：6255-6264.
T cells are known to cross-react with diverse peptide MHC Ags through their alpha beta TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-K-b and alloantigen QL9-L-d. In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3 alpha loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-K-b), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-L-d showed that CDR1, CDR2, and CDR3 beta conformations and docking orientations were remarkably similar. Although the CDR3 alpha loop of TCR m67 conferred a 2000-fold higher affinity for SIY-K-b, the TCR maintained the same docking angle on QL9-L-d as the 2C TCR. Thus, CDR3a dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation. The Journal of Immunology, 2008, 181: 6255-6264.