Transfection of major histocompatibility complex class I and class II genes causes tumour rejection.
Many human and mouse tumours do not express MHC class II antigens and have reduced levels of class I antigens. Because of the requirement for class I and/or class II antigen for antigen presentation to Th and Tc cells, these phenotypes may enable tumour cells to 'escape' the host's immune response. Experiments presented here are designed to assess the role of MHC class I and class II antigens in tumour immunity, and to overcome the MHC class I- or class II-negative phenotype. When transfected with the syngeneic H-2Db gene, the MHC antigen-negative 402AX teratocarcinoma expresses high levels of H-2Db antigen. 402AX/Db cells are rejected by MHC allogeneic and some MHC syngeneic 402AX-susceptible mice, however the fully syngeneic strain of origin (129) remains tumour-susceptible. Induction of MHC class I gene products on class I antigen-negative embryonal carcinoma cells therefore increases tumour immunogenicity in some hosts, but not in the fully syngeneic mouse. In an attempt to enhance antigen presentation of tumour-associated antigens to Th cells, MHC class I antigen-positive SaI (KkDd) sarcoma cells were transfected with syngeneic A alpha k and A beta k genes to generate Iak-expressing tumour cells. SaI/Ak cells are efficiently rejected by syngeneic A/J (KkDd) mice, while untransfected SaI cells are lethal. Induction of MHC class II antigen expression on the class I antigen-positive SaI sarcoma therefore completely abrogates malignancy.
Ostrand-Rosenberg
S
S
Department of Biology, University of Maryland, Baltimore 21228.
Clements
V K
VK
Thakur
A
A
Cole
G A
GA
D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology*; D013724:Teratoma / Q000276:immunology*; D014162:Transfection
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II