Engineered T-cell receptor tetramers bind MHC-peptide complexes with high affinity.
Engineered T-cell receptor tetramers bind MHC-peptide complexes with high affinity.
复制标题
工程化 T 细胞受体四聚体以高亲和力结合 MHC-肽复合物。
DOI：
10.1038/nbt1024
复制
发表时间：
2004
影响因子：
46.9
通讯作者：
Kuroda,MarceloJ
中科院分区：
文献类型：
--
作者：
Subbramanian,RamuA;Moriya,Chikaya;Martin,KristiL;Peyerl,FredW;Hasegawa,Atsuhiko;Naoi,Akira;Chhay,Heng;Autissier,Patrick;Gorgone,DarciA;Lifton,MichelleA;Kuus-Reichel,Kristine;Schmitz,JörnE;Letvin,NormanL;Kuroda,MarceloJ
在这项研究中，我们将四聚体技术扩展到T细胞受体（TCR）。我们在不存在辅助分子的情况下鉴定了TCR αβ对，确保了在四聚化后保持稳定结合特征的高亲和力TCR的分离。结合TCR四聚体的细胞的平均荧光强度的平行变化准确地反映了与I类分子结合的同源肽水平的微妙变化，使我们能够准确地评估一组肽与主要组织相容性复合体（MHC）的结合亲和力。I类。使用特异于Mamu-A * 01等位基因的TCR四聚体，我们从一个大的远交恒河猴队列中鉴定出表达这种限制性I类等位基因的动物。TCR四聚体应该有助于MHC-肽界面的分析，更一般地，有助于免疫治疗剂和疫苗的设计。
In this study we extend tetramerization technology to T-cell receptors (TCRs). We identified TCR αβ pairs in the absence of accessory molecules, ensuring isolation of high-affinity TCRs that maintain stable binding characteristics after tetramerization. Subtle changes in cognate peptide levels bound to the class I molecule were accurately reflected by parallel changes in the mean fluorescence intensity of cells that bound TCR tetramers, allowing us to accurately assess the binding affinity of a panel of peptides to major histocompatibility complex (MHC) class I. Using a TCR tetramer specific for theMamu-A*01allele, we identified animals expressing this restricting class I allele from a large cohort of outbred rhesus macaques. TCR tetramers should facilitate analysis of the MHC-peptide interface and, more generally, the design of immunotherapeutics and vaccines.