Cutting Edge: Monovalency of CD28 Maintains the Antigen Dependence of T Cell Costimulatory Responses1
Cutting Edge: Monovalency of CD28 Maintains the Antigen Dependence of T Cell Costimulatory Responses1
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最前沿：CD28 的单价性维持 T 细胞共刺激反应的抗原依赖性1
作者：
K. Dennehy;F. Elías;G. Zeder‐Lutz;Xin Ding;D. Altschuh;F. Lühder;T. Hünig
CD 28和CTLA-4是初始T细胞上的主要共刺激受体。但尚不清楚为什么CD 28是单价的，而CTLA-4对于它们共享的配体CD 80/86是二价的。我们通过将CTLA-4或CD 80的胞外结构域与CD 28的胞内结构域融合来产生二价CD 28构建体。将二价或单价⑶ 28构建体与重组配体连接，具有或不具有TCR共连接。单价CD 28连接不诱导应答，除非TCR被共连接。相比之下，二价CD 28连接在不存在TCR接合的情况下诱导应答。为了将这些发现扩展到原代细胞，我们使用了新型超激动剂和常规CD 28 Ab。超激动性Ab D 665而非常规Ab E18主要以低CD 28/Ab比率连接CD 28双链，并诱导Ag非依赖性T细胞增殖。因此，CD 28对其天然配体的单价性对于在不存在TCR接合的情况下提供共刺激而不诱导应答是必需的。
CD28 and CTLA-4 are the major costimulatory receptors on naive T cells. But it is not clear why CD28 is monovalent whereas CTLA-4 is bivalent for their shared ligands CD80/86. We generated bivalent CD28 constructs by fusing the extracellular domains of CTLA-4 or CD80 with the intracellular domains of CD28. Bivalent or monovalent CD28 constructs were ligated with recombinant ligands with or without TCR coligation. Monovalent CD28 ligation did not induce responses unless the TCR was coligated. By contrast, bivalent CD28 ligation induced responses in the absence of TCR engagement. To extend these findings to primary cells, we used novel superagonistic and conventional CD28 Abs. Superagonistic Ab D665, but not conventional Ab E18, predominantly ligates CD28 bivalently at low CD28/Ab ratios and induces Ag-independent T cell proliferation. Monovalency of CD28 for its natural ligands is thus essential to provide costimulation without inducing responses in the absence of TCR engagement.
T 细胞激活中的 CD28 连接：两种信号转导途径的证据。
影响因子：
20.3
作者：
Ledbetter,JA;Imboden,JB;Schieven,GL;Grosmaire,LS;Rabinovitch,PS;Lindsten,T;Thompson,CB;June,CH
通讯作者：
June,CH
影响因子：
32.4
作者：
Perez, VL;VanParijs, L;Abbas, AK
通讯作者：
Abbas, AK