The proposal has two main objectives: (1) To find out what general properties of tumor cell surface antigens provoke sensitization of thymus-derived killer cells (T killer) and what properties of cell surface antigens provoke sensitization of thymus-derived helper cells (T helper) and antibody synthesis. In the first series of experiments, the relationship between T helper and T killer cells will be explored. In the second series of experiments, the cytotoxic killer cells, arising during the immune response to allogeneic and xenogeneic tumor cells, will be studied to find out whether in response to allogeneic antigens T killer cells are generated, whereas in response to xenogeneic antigens T helper cells are generated. In the third series of experiments the killer cells in spleens sensitized to hapten or protein antigens, capable of lysing target cells to which the sensitizing antigen is coupled, will be characterized. This will elucidate whether T killer cells can be generated in response to hapten and protein antigens. (2) The second objective is to alter the immunogenicity of tumor cells in a controlled way such that cell-mediated rather than humoral immunity is elicited. DBA 2 mastocytoma P815 cells will be subjected to various degrees of acetoacetylation or fixation with formaldehyde or glutaraldehyde and tested for: (1) loss of antigenic determinants on their cell surface as assayed by quantitative absorption with specific antibody; (b) their immunogenicity in terms of allogeneic or syngeneic humoral and cell-mediated immunity in vitro and in vivo; (c) their usefulness as a tumor vaccine in protecting DBA 2 mice to a subsequent challenge of live tumor cells and in promoting rejection of residual tumor. Such methos, it is hoped, may suggest new approaches of vale in immunotherapy in a clinical situation.