T cell activation is initiated by signaling molecules downstream of the T cell receptor (TCR) that are organized by adaptor proteins. CIN85 (Cbl-interacting protein of 85 kDa) is one such adaptor protein. Here, we showed that CIN85 limited T cell responses to TCR stimulation. Compared to activated wild-type (WT) T cells, those that lacked CIN85 produced more IL-2 and exhibited greater proliferation. After stimulation of WT T cells with their cognate antigen, CIN85 was recruited to the TCR signaling complex. Early TCR signaling events, such as phosphorylation of ζ-chain–associated protein kinase 70 (Zap70), Src homology 2 (SH2) domain–containing leukocyte protein of 76 kDa (SLP76), and extracellular signal–regulated kinase (Erk), were enhanced in CIN85-deficient T cells. The inhibitory function of CIN85 required the SH3 and PR regions of the adaptor, which associated with the phosphatase suppressor of TCR signaling–2 (Sts-2) after TCR stimulation. Together, our data suggest that CIN85 is recruited to the TCR signaling complex and mediates inhibition of T cell activation through its association with Sts-2.

T细胞活化是通过信号转导由衔接蛋白组成的T细胞受体（TCR）下游分子开始的。CIN85（85kDa的Cbl相互作用蛋白）就是这样一种衔接蛋白。在这里，我们表明CIN85限制了T细胞对TCR刺激的反应。与活化的野生型（WT）T细胞相比，缺少CIN85的T细胞产生更多的IL-2，并表现出更大的增殖。用它们的同源抗原刺激WT T细胞后，将CIN85募集到TCR信号复合物中。早期的TCR信号事件包括ζ链相关蛋白激酶70（Zap70）的磷酸化，含Src同源2（SH2）域的76 kDa白细胞蛋白（SLP76）和细胞外信号调节激酶（Erk）。在CIN85缺陷型T细胞中增强。CIN85的抑制功能需要衔接子的SH3和PR区，这与TCR刺激后TCR信号传导-2（Sts-2）的磷酸酶抑制剂有关。在一起，我们的数据表明CIN85被招募到TCR信号复合物，并通过与Sts-2的结合介导T细胞活化的抑制作用。