INDIVIDUAL-DIFFERENCES IN THE ORIENTATION OF THE CYTOLYTIC T-CELL RESPONSE AGAINST MOUSE-TUMOR P815

We reported previously that the mouse tumor P815 expresses four distin ct antigens (A, B, C, D) recognized by syngeneic cytolytic T lymphocyt es (CTL). A fifth P815 antigen (E) was identified by means of a CTL do ne derived from tumor-infiltrating lymphocytes. We compared a number o f mice for the orientation of their CTL response with respect to the v arious P815 antigens. Lymphocytes from mice inoculated subcutaneously with living P815 cells were stimulated in vitro with tumor cells and t he resulting CTL were tested against targets expressing either antigen s A and B or antigens C, D and E. Many mice had an asymmetrical respon se, some producing CTL directed almost exclusively against antigens A, B and others producing CTL directed almost exclusively against C, D. E. When mice were inoculated into two separate sites, different orient ations in the responses of the two local lymph nodes were often observ ed, suggesting that individual differences in the orientation of the a nti-P815 CTL response do not result from preexisting differences betwe en the animals. Asymmetrical CTL responses persisted in mice that were given a second injection of tumor cells. A possible interpretation of our results is that the major component of the CTL response is made o f the progeny of a very small number of CTL precursors that happen to be the first to be stimulated by the tumor antigens.