SPECIFIC T-HELPER CELL REQUIREMENT FOR OPTIMAL INDUCTION OF CYTOTOXICT-LYMPHOCYTES AGAINST MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II NEGATIVE TUMORS

This study shows that induction of tumor-specific CD4(+) T cells by va ccination with a specific viral T helper epitope, contained within a s ynthetic peptide, results in protective immunity against major histoco mpatibility complex (MHC) class II negative, virus-induced tumor cells . Protection was also induced against sarcoma induction by acutely tra nsforming retrovirus. In contrast, no protective immunity was induced by vaccination with an unrelated T helper epitope. By cytokine pattern analysis, the induced CD4(+) T cells were of the T helper cell 1 type . The peptide-specific CD4(+) T cells did not directly recognize the t umor cells, indicating involvement of cross-priming by tumor-associate d antigen-presenting cells. The main effector cells responsible for tu mor eradication were identified as CD8(+) cytotoxic T cells that were found to recognize a recently described immunodominant viral gag-encod ed cytotoxic T lymphocyte (CTL) epitope, which is unrelated to the vir al env-encoded T helper peptide sequence. Simultaneous vaccination wit h the tumor-specific T helper and CTL epitopes resulted in strong syne rgistic protection. These results indicate the crucial role of T helpe r cells for optimal induction of protective immunity against MHC class II negative tumor cells. Protection is dependent on tumor-specific CT Ls in this model system and requires cross-priming of tumor antigens b y specialized antigen-presenting cells. Thus, tumor-specific T helper epitopes have to be included in the design of epitope-based vaccines.