ZETA-PHOSPHORYLATION WITHOUT ZAP-70 ACTIVATION-INDUCED BY TCR ANTAGONISTS OR PARTIAL AGONISTS
ZETA-PHOSPHORYLATION WITHOUT ZAP-70 ACTIVATION-INDUCED BY TCR ANTAGONISTS OR PARTIAL AGONISTS
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DOI：
10.1126/science.7824949
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发表时间：
1995-01-27
期刊：
影响因子：
56.9
通讯作者：
GERMAIN, RN
中科院分区：
文献类型：
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作者：
MADRENAS, J;WANGE, RL;GERMAIN, RN
抗原特异性T细胞受体（TCR）识别的肽-主要组织相容性复合物（MHC）分子配体的微小变化可以将完全活化的复合物转化为部分活化甚至抑制性复合物。拮抗剂和几种部分激动剂都刺激了ζ链磷酸化的不同模式并且不能激活相关的ZAP-70激酶，这些结果确定了早期酪氨酸磷酸化级联中的一个特定步骤，该步骤在TCR与修饰的肽-MHC分子复合物接合后发生改变，这一发现可以解释这些变体配体对TCR占据的不同生物学反应。
Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones, This study examined early TCR-dependent signals induced by such partial agonists or antagonists, In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of zeta chain phosphorylation and failed to activate associated ZAP-70 kinase, These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes, This finding may explain the different biological responses to TCR occupancy by these variant ligands.