Rejection of Tumors by MHC Class Ib-Restricted CTL

描述（由申请人提供）：已观察到Q9（一种鼠非多态性非经典Ib类MHC分子）在所有表达Q9的小鼠品系来源的肿瘤细胞系中下调或丢失。此外，已发现Q9赋予宿主动物免受黑素瘤肿瘤攻击的保护。本申请的重点是确定Q9是否作为同基因肿瘤反应性CTL的限制性元件起作用。所提出的实验旨在建立用于确定CTL参与Q9介导的模型肿瘤排斥和用于产生高效抗肿瘤CTL的方案，以提供这些CTL的详细表征，并评估在Q9背景下呈递的潜在肿瘤相关抗原。用于实现这些目标的方法将包括体外细胞毒性测定、流式细胞术分析、微阵列分析、激光捕获显微镜、实时定量PCR和蛋白质纯化。这些研究可能导致通用肽疫苗的开发，从而为癌症的治疗做出重大贡献。与Q9模型Ib类抗原的工作也将为未来与人类I类MHC如HLA-C和/或HLA-E、-F、-G或其他尚未发现的I类分子的研究奠定基础。

DESCRIPTION (provided by applicant): Q9, a murine non-polymorphic nonclassical class Ib MHC molecule, has been observed to be downregulated or lost in all Q9-expressing mouse strain-derived tumor cell lines. Furthermore, Q9 has been found to confer protection to host animals from melanoma tumor challenge. The focus of this application is to determine if Q9 functions as a restriction element for syngeneic tumor-reactive CTLs. The proposed experiments aim to establish protocols for the determination of CTL participation in Q9-mediated rejection of model tumors and for the generation of highly potent antitumor CTLs, to provide a detailed characterization of these CTLs, and to evaluate potential tumor-associated antigens that are presented in the context of Q9. Methods used to achieve these aims will include in vitro cytotoxicity assays, flow cytometry analyses, microarray analyses, laser capture microscopy, real-time quantitative PCR and protein purification. These studies may lead to the development of universal peptide vaccines, thereby providing a significant contribution to the treatment of cancers. Work with the Q9 model class Ib antigen will also lay a foundation for future studies with human class I MHC such as HLA-C and/or HLA-E, -F, -G or other yet undiscovered class I molecules.