Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: Insights into MHC bias and antigen specificity
Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: Insights into MHC bias and antigen specificity
复制标题
DOI：
10.1016/j.immuni.2004.11.015
复制
发表时间：
2005-01-01
期刊：
影响因子：
32.4
通讯作者：
Garcia, KC
中科院分区：
文献类型：
--
作者：
Maynard, J;Petersson, K;Garcia, KC
T细胞受体与不同多肽配体的交叉反应和对MHC的偏向识别是抗原识别的耦合特征，这是T细胞不同功能所必需的。在一个自身反应的EAE T细胞克隆172.10和11类MHC I-A(U)提出的髓鞘碱性蛋白(1-11)之间的晶体结构中，MHC的识别由TCR的Vbeta结构域主导，它以一种暗示生殖系编码的TCR/MHC“锚点”的方式与MHCα链相互作用。值得注意的是，TCR CDR3环和MBP多肽之间几乎没有特定的接触。我们还发现，从组合文库中提取的超过100万个不同的多肽可以激活172.10，但TCR强烈倾向于天然的MBP接触残基。我们认为，虽然pMHC的TCR扫描可能由于对MHC的TCR种系偏见而退化，但识别结构不同的激动肽并不表明TCR混杂，而是TCR参与的高度特异性的替代解决方案。
T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class 11 MHC I-A(u), recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.