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Immunotherapy with Dendritic Cells and Tumor Major Histocompatibility Complex Class I-derived Peptides Requires a High Density of Antigen on Tumor Cells¹

Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington South, New Zealand [P. R., I. F. H., S. P. H., J. M. R., F. R.], and Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany [H. P.]

Immunization with dendritic cells and unfractionated MHC class I-binding peptides derived from autologous tumor cells has been shown to induce effective antitumor immunity. However, the importance of the relative abundance of tumor peptides on the surface of tumor cells is not known. We have addressed this question using peptides isolated from three tumor cell lines transfected with a minigene encoding amino acids 33–41 of the lymphocytic choriomeningitis virus glycoprotein (LCMV_33–41). The three cell lines expressed different levels of MHC class I molecules and had different abilities to stimulate proliferation of LCMV_33–41-specific T cells in vitro. We found that antitumor immune responses were best elicited by immunizing mice with dendritic cells and synthetic LCMV_33–41 peptide. Peptide preparations from a given tumor cell line conferred protection against challenge with the same tumor cell line. However, protective immunity to a different tumor could be induced only if the cell line used for peptide preparation presented a high relative proportion of LCMV_33–41 in association with MHC class I. Our results suggest that multiple peptide epitopes are required for the induction of an effective antitumor immune response using MHC class I-binding peptides from tumor cells. Also, the ability to induce an antitumor immune response appears to correlate with the proportion, rather than the absolute amount, of tumor-specific peptide in the mixture used for immunization.

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