title: Expression of multiple unique rejection antigens on murine leukemia BALB/c RLmale symbol1 and the role of dominant Akt antigen for tumor escape.
abstract: Using the pRL1a Ag-loss RLmale symbol1 tumor variant cell line RM2-1, we demonstrated the presence of tumor Ags other than pRL1a that were recognized by CTLs on RLmale symbol1 cells. Semiallogeneic CB6F1 or syngeneic BALB/c CTLs generated against RM2-1 lysed RM2-1 and RLmale symbol1 cells to a similar extent, but no killing was observed with any other tumor or normal cells examined. Clonal analysis and sensitization with reversed phase-HPLC fractions revealed that there were Dd- and Ld-binding peptides recognized by RM2-1 CTLs. Lysis by bulk CTLs stimulated against RLmale symbol1 and limiting dilution analysis suggested that the pRL1a peptide was dominantly recognized to the RM2-1 peptides by CTLs on RLmale symbol1 cells. The rejection response against the parental RLmale symbol1 tumor was much less than that against RM2-1 cells in either CB6F1 or BALB/c mice, suggesting that the presence of altered Akt molecules from which the dominant pRL1a peptide was derived inhibited the rejection response against RLmale symbol1. Depletion of CD4 T cells caused the regression of RLmale symbol1 at the doses in which the tumor grew in untreated mice. The generation of pRL1a CTLs was inhibited in RLmale symbol1-bearing mice. Thus, immunoregulatory CD4 T cells were most likely activated by the altered Akt molecules and inhibited the efficient generation of CTLs against the dominant pRL1a Ag in RLmale symbol1.
authors.affiliation: Department of Parasitology and Immunology, Okayama University Medical School, Okayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Honda
authors.forename: I
authors.initials: I
authors.lastname: Tawara
authors.forename: A
authors.initials: A
authors.lastname: Uenaka
authors.forename: T
authors.initials: T
authors.lastname: Kanematsu
authors.forename: E
authors.initials: E
authors.lastname: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000096:biosynthesis* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D002999:Clone Cells; D003433:Crosses, Genetic; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005799:Genes, Dominant / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007271:Injections, Intradermal; D007942:Leukemia, Experimental / Q000276:immunology*; D007953:Leukemia, Radiation-Induced / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010455:Peptides / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D010455:Peptides; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt