Negative selection of CD4+ CD8+ thymocytes by T-cell receptor peptide antagonists.

Negative selection of CD4+ CD8+ thymocytes by T-cell receptor peptide antagonists.
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T 细胞受体肽拮抗剂对 CD4 CD8 胸腺细胞的负选择。

DOI:
10.1073/pnas.91.9.4057
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发表时间:
1994
影响因子:
11.1
通讯作者:
Grey,HM
Grey,HM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Page,DM;Alexander,J;Snoke,K;Appella,E;Sette,A;Hedrick,SM;Grey,HM

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抗原诱导的T细胞活化可被称为T细胞受体肽拮抗剂的抗原类似物特异性抑制。这些拮抗剂似乎通过诱导T细胞受体和呈递肽的主要组织相容性复合物分子之间形成非刺激性或部分刺激性复合物来起作用。在此,我们研究了T细胞受体肽拮抗剂对胸腺细胞负选择的影响。首先,鉴定了细胞色素c特异性T细胞克隆AD10的肽拮抗剂。然后使用来自AD 10 T细胞受体转基因小鼠的胸腺细胞,在体外模型系统中测试这些肽诱导阴性选择的能力。虽然不能诱导成熟T细胞活化,但T细胞受体肽拮抗剂诱导了CD4+ CD8+胸腺细胞的缺失。这些结果表明,CD 4 + CD 8+胸腺细胞的负选择可以由亲和力低于成熟T细胞活化所需亲和力的T细胞受体相互作用诱导。
Antigen-induced activation of T cells can be specifically inhibited by antigen analogs that have been termed T-cell receptor peptide antagonists. These antagonists appear to act by inducing the formation of nonstimulatory or partially stimulatory complexes between T-cell receptors and the major histocompatibility complex molecules presenting the peptides. Herein, we have investigated the effect of T-cell receptor peptide antagonists on thymocyte negative selection. First, peptide antagonists were identified for the cytochrome c-specific T-cell clone AD10. These peptides were then tested for their ability to induce negative selection in an in vitro model system using thymocytes from mice transgenic for the AD10 T-cell receptor. Though unable to induce mature T-cell activation, the T-cell receptor peptide antagonists induced deletion of CD4+ CD8+ thymocytes. These results suggest that negative selection of CD4+ CD8+ thymocytes can be induced by T-cell receptor interactions of a lower affinity than those required for mature T-cell activation.
DOI: 10.1038/355224a0
发表时间: 1992-01-16
期刊: NATURE
影响因子: 64.8
作者:
JORGENSEN, JL;ESSER, U;DAVIS, MM
通讯作者: DAVIS, MM