Generation of antigenic variants from a nonantigenic murine tumor cell line by transfection with a gene encoding a novel tumor-specific transplantation antigen.
Tumors induced in mice by UV radiation often express highly immunogenic tumor-specific transplantation antigens (TSTA). The 216 gene, which encodes a TSTA of the C3H tumor UV-1591, has been cloned and characterized as a novel major histocompatibility complex Class I antigen. The purpose of this study was to determine whether the 216 gene-encoded TSTA can function as a tumor rejection antigen when expressed on unrelated, nonantigenic murine tumor cells or whether its function is restricted to UV-induced tumors. A cell line (10T-1) derived from a spontaneous transformant of C3H 10T1/2 cells was cotransfected with DNA from p216 and pSV2-neo plasmids. About 2 wk after transfection, G418-resistant colonies were isolated randomly and tested for cell surface expression of the 216 gene product using a monoclonal antibody specific for 216 gene-encoded TSTA. Of 20 clones tested, four expressed high levels of 216 gene-encoded TSTA. These four clones were highly antigenic in that they were completely rejected in normal mice but grew progressively in nude mice. Furthermore, the 216-positive clones were immunologically cross-reactive with UV-1591, as determined by in vitro cytotoxic T-lymphocyte and in vivo immunization and challenge assays. Surprisingly, 216-positive 10T-1 transfectants also cross-reacted with 10T-1 cells, both in vitro and in vivo. These results demonstrate that the product of a cloned TSTA gene from a UV-induced murine tumor is capable of functioning as a tumor rejection antigen when expressed on unrelated, nonantigenic tumor cells. In addition, these results indicate that this approach could be used to augment the immune response against poorly antigenic tumors.
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
D S
DS
Kaba
B W
BW
McIntyre
M L
ML
Kripke
R S
RS
Goodenow
H
H
Schreiber
H N
HN
Ananthaswamy
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology*; D009381:Neoplasms, Radiation-Induced / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen