St-Pierre Y, Nabavi N, Ghogawala Z, Glimcher L H, Watts T H
Department of Immunology, University of Toronto, Ontario, Canada.
J Immunol. 1989 Aug 1;143(3):808-12.
B cell transfectants expressing MHC class II (Ia) molecules with truncated cytoplasmic domains are defective in both antigen presentation and in anti-Ia induced intracellular signaling. In this report we show that the Ag presentation defect in a truncated-Ia expressing transfectant can be overcome by providing the second messenger for the Ia-mediated signaling event. Preincubation with dibutyryl-cAMP restored the ability of the truncated Ia expressing-transfectant to stimulate IL-2 release by otherwise nonresponsive T hybrids. This provides direct functional evidence that signaling via the cytoplasmic domains of MHC class II proteins leads to the generation of accessory signals in the B cell that are important in T cell activation. The dibutyryl-cAMP induced signal must be on the same cell as the restricting element, does not bypass the requirement for occupancy of the T cell receptor with its normal ligand, and is lost upon fixation of the cells. Thus T cell-B cell interaction involves a two way communication in which both cells sense and respond to the formation of the antigen/MHC/TCR complex.
表达具有截短细胞质结构域的MHC II类（Ia）分子的B细胞转染子在抗原呈递和抗Ia诱导的细胞内信号传导方面均存在缺陷。在本报告中，我们表明，通过为Ia介导的信号事件提供第二信使，可以克服表达截短Ia的转染子中的抗原呈递缺陷。用二丁酰环磷腺苷（dibutyryl-cAMP）预孵育可恢复表达截短Ia的转染子刺激原本无反应的T杂交瘤释放白细胞介素-2的能力。这提供了直接的功能证据，即通过MHC II类蛋白的细胞质结构域进行信号传导会导致B细胞中产生辅助信号，这些信号在T细胞活化中很重要。二丁酰环磷腺苷诱导的信号必须与限制元件在同一细胞上，不能绕过T细胞受体被其正常配体占据的要求，并且在细胞固定后会消失。因此，T细胞与B细胞的相互作用涉及双向通讯，其中两个细胞都能感知并响应抗原/MHC/TCR复合物的形成。
