Ostrand-Rosenberg S, Roby C A, Clements V K
University of Maryland Baltimore County, Department of Biological Sciences 21228.
J Immunol. 1991 Oct 1;147(7):2419-22.
Transfection of syngeneic MHC class II genes into the lethal mouse SaI tumor abrogates the malignancy of the tumor in the autologous host, and protects the host against subsequent challenges with the wild type class II- tumor. We have hypothesized that the transfectants induce protective immunity by functioning as APC for tumor peptides, and stimulating tumor-specific Th cells. Recent in vitro studies suggest that Ag presentation by class II-restricted APC requires the cytoplasmic domain of the class II molecule, and may involve intracellular signaling via the cytoplasmic domain. To determine if the class II cytoplasmic domain is required for enhanced tumor-specific immunity, SaI mouse sarcoma cells were transfected with syngeneic Aak and Abk genes with truncated cytoplasmic domains. These transfectants are as malignant as wild type class II- SaI cells in autologous A/J mice. Stimulation of tumor-specific immunity by class II+ tumor cells is therefore dependent on the class II cytoplasmic region, and may involve intracellular signaling events.
将同基因的MHC II类基因转染到致死性小鼠SaI肿瘤中，可消除该肿瘤在自体宿主中的恶性程度，并保护宿主免受野生型II类肿瘤随后的攻击。我们推测，转染子通过作为肿瘤肽的抗原呈递细胞并刺激肿瘤特异性Th细胞来诱导保护性免疫。最近的体外研究表明，II类限制性抗原呈递细胞的抗原呈递需要II类分子的胞质结构域，并且可能涉及通过胞质结构域的细胞内信号传导。为了确定增强肿瘤特异性免疫是否需要II类胞质结构域，用具有截短胞质结构域的同基因Aak和Abk基因转染SaI小鼠肉瘤细胞。这些转染子在自体A/J小鼠中与野生型II类SaI细胞一样具有恶性。因此，II类阳性肿瘤细胞对肿瘤特异性免疫的刺激取决于II类胞质区域，并且可能涉及细胞内信号传导事件。
