In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses.

The gag membrane protein gP85gag, encoded by Moloney murine leukemia virus (M-MLV), was identified as a target molecule recognized by Moloney murine sarcoma virus--M-MLV (M-MSV--M-MLV)-specific cytolytic T lymphocyte (CTL) clones. Target cells infected with Ab-X-MLV, an M-MLV-derived mutant virus not encoding gP85gag, were not lysed by the CTL clones. The same CTL clones were shown previously to induce the destruction of M-MLV-induced tumor cells in the peritoneal cavity. We have now characterized CTL-resistant antigen-loss tumor cell variants that have lost the surface antigen, but which retain transcriptionally silent M-MLV genomes. A cloned antigen-loss variant that reverted in vitro to the CTL-susceptible phenotype reexpressed M-MLV genomes that had undergone an insertion event in the region of the viral DNA coding for the gag membrane protein. Intravenous injection of virus-specific CTL clones inhibited tumor formation in mice injected subcutaneously with M-MSV--M-MLV.

Section: A O T Bmentioning

confidence: 99%

Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo.

Hoorn¹,

Lahaye²,

Müller³

et al. 1985

“…It remains to be determined whether the basis for such a high degree of restriction to H-2D b is related to the selective incorporation of H-2D b molecules into the virion envelope (25). In view of a recent report that suggested that intact virus could substitute for tumor cells in the generation of MoLV-specific CTL in mass culture (26), experiments are in progress to examine if viral preparations can be used as a source of antigen for the isolation and maintenance of CTL clones. Summary Cytolytic T lymphocyte (CTL) clones specific for Moloney leukemia virus (MoLV)derived tumor cells were generated by placing limiting numbers ofC57BL/6 responder cells into mixed leukocyte-tumor cell microcultures.…”

Section: Reactivity Pattern Of Mol V-specific Ctl Clonesmentioning

confidence: 99%

Antigenic specificity of the cytolytic T lymphocyte response to murine sarcoma virus-induced tumors. III. Characterization of cytolytic T lymphocyte clones specific for Moloney leukemia virus-associated cell surface antigens.

Weiss¹,

Brunner²,

MacDonald³

et al. 1980

Cytolytic T lymphocyte (CTL) clones specific for Moloney leukemia virus (MoLV)-derived tumor cells were generated by placing limiting numbers of C57BL/6 responder cells into mixed leukocyte-tumor cell microcultures. Under appropriate conditions (presence of stimulating tumor cells, accessory cells, and T cell growth factor), such cloned CTL could readily be expanded to provide large numbers of homogeneous, highly cytolytic CTL populations for further characterization. Using four target-cell types, three specificity patterns were observed: one reactive with the syngeneic MoLV-derived tumor only, one cross-reactive with an allogeneic MoLV-derived tumor, and one cross-reactive with normal allogeneic cells. Subclones derived from these three types of clones exhibited a high degree of stability in terms of lytic activity and specificity over a 4-mo period of observation. Three clones analyzed by flow cytofluorometry using monoclonal antibodies were all found to be of the Lyt-1+2+ phenotype. Furthermore, lysis of target cells by all of six clones tested was inhibited by anti-H-2Db (but not by anti-H-2Kb) monoclonal antibodies, demonstrating H-2Db-restriction at the clonal level.

“…Identical results were obtained with these two leukemias, indicating that expression of individually distinct antigens is not restricted to a rare leukemia. Cytotoxic T cells generated against murine leukemia virus (MuLV)-induced leukemias have been reported to recognize antigens shared by several leukemias induced by the same virus (8)(9)(10)(11)(12), predominantly type-or subgroup-specific determinants of gp70 or other viral structural components (8)(9)(10)(11). Compared with the extensive information that exists regarding the specificity of T cell recognition of leukemias induced by Gross and Moloney MuLV, very little is known about RadLV-induced leukemias.…”

Section: Discussionmentioning

confidence: 99%

Cell surface antigens of murine leukemias induced by radiation leukemia virus. Recognition of individually distinct cell surface antigens by cytotoxic T cells on leukemias expressing crossreactive transplantation antigens.

Morishita¹,

Shiku²,

Horibe³

et al. 1986

Antigens specific for individual tumors were first discovered in experiments that showed the rejection of chemically induced sarcomas in mice and rats that had been immunized with the same tumor (1). Subsequently, individually distinct antigens were also found in transplantation studies of murine reticulum cell sarcomas and mammary tumors. Detailed study of these unique antigens has long been hampered by the considerable difficulties encountered in attempts to detect them in vitro. Success was first reported in a study of the methylcholanthrene-induced BALB/c sarcoma Meth A. Hyperimmunization ofsyngeneic mice with this tumor resulted in the production of antibodies recognizing a cell surface antigen whose expression showed the same restriction as the antigen detected in transplantation experiments (2). More recent serological studies of feline leukemias, and of murine sarcomas induced by the Rous sarcoma virus, have also defined individually distinct cell surface antigens expressed only on the tumor used for immunization. With the advances in the serological analysis of human tumors brought about by the development of autologous typing, unique cell surface antigens have also been found on human cancers--melanoma, astrocytoma, and renal cancer (2).Although individually distinct tumor antigens were initially shown in transplantation experiments generally considered to reflect cellular immunity, there have only been a few reports describing recognition of unique tumor antigens by cytotoxic T cells in vitro (3, 4). We report here that leukemias induced in mice by the radiation leukemia virus (RadLV) express individually distinct antigens recognized by cytotoxic T cells, in addition to crossreacting tumorspecific antigens detected in transplantation experiments.