Protective immunity against disparate tumors is mediated by a nonpolymorphic MHC class I molecule.
Current peptide-based immunotherapies for treatment of model cancers target tumor Ags bound by the classical MHC class I (class Ia) molecules. The extensive polymorphism of class Ia loci greatly limits the effectiveness of these approaches. We demonstrate in this study that the murine nonpolymorphic, nonclassical MHC class I (class Ib) molecule Q9 (Qa-2) promotes potent immune responses against multiple syngeneic tumors. We have previously shown that ectopic expression of Q9 on the surface of class Ia-negative B78H1 melanoma led to efficient CTL-mediated rejection of this tumor. In this study, we report that surface-expressed Q9 on 3LLA9F1 Lewis lung carcinoma and RMA T cell lymphoma also induces potent antitumor CTL responses. Importantly, CTL harvested from animals surviving the initial challenge with Q9-positive 3LLA9F1, RMA, or B78H1 tumors recognized and killed their cognate tumors as well as the other cancer lines. Furthermore, immunization with Q9-expressing 3LLA9F1 or RMA tumor cells established immunological memory that enhanced protection against subsequent challenge with a weakly immunogenic, Q9-bearing melanoma variant. Collectively, the generation of cross-reactive CTL capable of eliminating multiple disparate Q9-expressing tumors suggests that this nonpolymorphic MHC class I molecule serves as a restriction element for a shared tumor Ag(s) common to lung carcinoma, T cell lymphoma, and melanoma.
Chiang
Eugene Y
EY
Center for Immunology, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Stroynowski
Iwona
I
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000517:prevention & control; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000517:prevention & control; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007108:Immune Tolerance / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000517:prevention & control; D008544:Melanocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens