Abstract
After mutagenesis of mouse mastocytoma P815, it is possible to obtain variant (tum^−^) clones that are almost always rejected by syngeneic DBA/2 mice. Most tum^−^ clones express new variant‐specific antigens that can be detected by cytolytic T cells (CTL). Occasionally, mice injected with tum^−^ variants eventually develop progressive tumors. Cells from these tumors were analyzed for antigen expression with variant‐specific and P815‐specific CTL clones. Out of 13 tumors examined, 11 were composed of cells that had clearly lost a variant‐specific antigenic determinant. These results indicate that tum^−^ variants induce a specific host rejection response which usually results in complete elimination of the variant cells, but that occasional antigen‐loss constitutes an important mechanism of escape. The loss of a variant‐specific antigenic determinant from one tum^−^ clone that had escaped rejection allowed the detection of a residual variant‐specific determinant. This was demonstrated by isolating a new CTL clone that lysed both the original tum^−^ clone and its antigen‐loss variant, but not other P815 targets. Thus, some complex transplantation antigens can be separated into independent determinants by using antigen‐loss variants.