CD8(- REQUIREMENT FOR TUM(-) OR HELPER PEPTIDES IN PRIMING FOR SKIN-TEST REACTIVITY TO A P815AB-RELATED PEPTIDE() CELL ACTIVATION TO A MAJOR MASTOCYTOMA REJECTION ANTIGEN, P815AB )

Delayed-type hypersensitivity (DTH) responses, mediated by CD8(+) cell s and detected by skin test assay, occur in sensitized mice in respons e to challenge with class I-restricted antigenic peptides of mutageniz ed (tum(-)) P815 mastocytoma cells. In contrast, a nonapeptide related to a tumor rejection antigen, P815AB, failed in this study to elicit DTH after sensitization of mice with irradiated tumor cells or adoptiv e transfer of P815AB-pulsed dendritic cells. Unresponsiveness, however , could be overcome by immunization with tumor cells co-expressing P81 5AB and tum(-) antigens. When used for cell pulsing in vitro, a mixtur e of P815AB and tum(-) peptides was also highly effective in inducing anti-P815AB reactivity, as was the combined use of P815AB and class II -restricted peptides of tetanus toxin or Plasmodium berghei circumspor ozoite protein. While the effector phase of the CD8(+) cell-mediated D TH to P815AB was unaffected by the ablation of CD4(+) cells, the same treatment, or neutralization of IFN-gamma, negated the induction of re activity if it occurred at the time of sensitization. Thus, defective activation of CD4(+) cells may contribute to the poor immunogenicity o f P815AB. Besides providing an insight into the mechanisms of anti-tum or protection induced by tum(-) cells, these data offer useful informa tion for the design of vaccination strategies against identified tumor antigens.