Rejection of Tumors by MHC Class Ib-Restricted CTL

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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.