Expression of multiple unique rejection antigens on murine leukemia BALB cRL male 1 and the role of dominant Akt antigen for tumor escape

Using the pRL1a Ag-loss RL male 1 tumor variant cell line RM2-1, we demonst rated the presence of tumor Ags other than pRL1a that were recognized by CT Ls on RL male 1 cells, Semiallogeneic CB6F(1) or syngeneic BALB/c CTLs gene rated against RM2-1 lysed RM2-1 and RL male 1 cells to a similar extent, bu t no killing was observed with any other tumor or normal cells examined. Cl onal analysis and sensitization with reversed phase-HPLC fractions revealed that there were D-d-and L-d-binding peptides recognized by RM2-1 CTLs, Lys is by bulk CTLs stimulated against RL male 1 and limiting dilution analysis suggested that the pRL1a peptide was dominantly recognized to the RM2-1 pe ptides by CTLs on RL male 1 cells, The rejection response against the paren tal RL male 1 tumor was much less than that against RM2-1 cells in either C B6F(1) or BALB/c mice; suggesting that the presence of altered Akt molecule s from which the dominant pRL1a peptide was derived inhibited the rejection response against RL male 1. Depletion of CD4 T cells caused the regression of RL male 1 at the doses in which the tumor grew in untreated-mice. The g eneration of pRL1a CTLs was inhibited in RL male 1-bearing mice. Thus, immu noregulatory CD4 T cells were most likely activated by the altered Akt mole cules and inhibited the efficient generation of CTLs against, the dominant pRL1a Ag in RL male 1.