Immunotherapy with dendritic cells and tumor major histocompatibility complex class I-derived peptides requires a high density of antigen on tumor cells

Immunization with dendritic cells and unfractionated MHC class I-binding pe ptides derived from autologous tumor cells has been shown to induce effecti ve antitumor immunity. However. the importance of the relative abundance of tumor peptides on the surface of tumor cells is not known. We have address ed this question using peptides isolated from three tumor cell lines transf ected with a minigene encoding amino acids, 33-41 of the lymphocytic chorio meningitis virus glycoprotein (LCMV33-41). The three cell lines expressed d ifferent levels of MHC class I molecules and had different abilities to sti mulate proliferation of LCMV33-41-specific T cells in vitro. We found that antitumor immune responses were best elicited by immunizing mice with dendr itic cells and synthetic LCMV33-41 peptide. Peptide preparations from a giv en tumor cell line conferred protection against challenge with the same tum or cell line. However, protective immunity to a different tumor could be in duced only if the cell line used for peptide preparation presented a high r elative proportion of LCMV33-41 in association with MHC class I. Our result s suggest that multiple peptide epitopes are required for the induction of an effective antitumor immune response using MHC class I-binding peptides f rom tumor cells. Also, the ability to induce an antitumor immune response a ppears to correlate with the proportion, rather than the absolute amount, o f tumor-specific peptide in the mixture used for immunization.