title: H-2 antigens and tumour-associated transplantation antigens in clones derived from a methylcholanthrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response.
abstract: The methylcholanthrene GR9 tumour is a fibrosarcoma, originated in a BALB/c (H-2d) mouse, composed of different clones (A7, G2, D8, D6, B11, B3, B7, C11, B10, B9) with different class I (Kd Dd Ld) expression. We present data indicating that MHC class I differences observed between the different clones correlated with RNA levels and can be modified with recombinant interferon-gamma. We also studied the presence of tumour-associated antigens in GR9 and their different clones using the monoclonal antibody (MoAb) technology. We produced two syngeneic MoAbs, A7.2 and A7.6, which reacted to GR9 clones. These MoAbs precipitated a 70-kilodalton molecule and did not react with cells positive for the classical Gp70 antigen such as YC-8, LSTRA (H-2d) and RBL-5 (H-2b) lymphomas. A7.2 and A7.6 MoAbs were also negative with normal cells. In this well-characterized tumour model, we analysed the influence of the expression of class I molecules and tumour-associated antigens upon the generation, in vitro and in vivo, of the specific anti-tumour immune response. We produced syngeneic anti-GR9 A7 cytotoxic T lymphocytes (CTLs) which showed significant cytotoxicity against most of the GR9 clones including clones with low or no H-2 class I expression. These CTLs showed no cytotoxic activity against other tumour cells and concanavalin A blasts, neither could the CTL-specific response be inhibited with A7.2 and A7.6 syngeneic MoAbs nor with a panel of anti-class I MoAbs. In vivo experiments have shown that pre-immunization with the immunogenic clone GR9 A7 protects against a challenge of the different GR9 clones, independently of their class I expression and their in vitro susceptibility to lysis by anti-GR9 A7 CTLs. These results demonstrate the existence of cross-reactive tumor-associated transplantation antigens between different clones of the same tumour and the absence of correlation between in vitro susceptibility to lysis and in vivo tumour rejection. Finally, we discuss these results in the context of anti-tumour effector mechanisms generated in chemically induced tumours.
authors.affiliation: Servicio Análisis Clínicos e Immunología, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pérez
authors.forename: A
authors.initials: A
authors.lastname: Garrido
authors.forename: I
authors.initials: I
authors.lastname: Algarra
authors.forename: A
authors.initials: A
authors.lastname: Caballero
authors.forename: C
authors.initials: C
authors.lastname: Delgado
authors.forename: M D
authors.initials: MD
authors.lastname: Collado
authors.forename: E
authors.initials: E
authors.lastname: Fernández-Cruz
authors.forename: F
authors.initials: F
authors.lastname: Garrido
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D008748:Methylcholanthrene