Induction of CD8+ Cytotoxic T Lymphocytes With MHC Class I Restriction by a Soluble Truncated Oncoprotein

概要

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CD8+ cytotoxic T lymphocytes (CTLs), which play a major role in the immunological defense against cancer, recognize endogenously produced peptides in the context of MHC class I molecules. We investigated how to induce CD8+ CTL responses against the HER2/neu/c-erbB2 (HER2) oncoprotein often overexpressed in a wide range of human adenocarcinomas. The immunization of BALB/c mice with a syngeneic cell line transduced with HER2 cDNA led to a successful induction of CD8+ CTLs which specifically destroyed HER2-expressing tumor cells. The CTLs recognized the HER2-derived peptide 1 (TYLPTNASL, pos. 63rd-71st amino acid) in the context of MHC class I Kd. The immunization of mice with a truncated HER2 oncoprotein containing 144 amino acids of HER2 (N terminus to 144th amino acid) failed to elicit measurable CTL activity for HER2-expressing target cells. We reconstituted the truncated HER2 protein into a mannan-coated liposome, and complexed the protein with a cholesterol-bearing mannan polysaccharide respectively. Both of these complexes were capable of inducing killer cells specific for HER2-expressing cells in murine model after immunization. These killer cells are Kd restricted CD8+ CTLs which recognize peptide 1. The cholesterol-bearing mannan polysaccharide facilitated the induction of specific CD8+ CTLs by an exogenous HER2 oncoprotein, and may therefore be useful in the development of cancer vaccines.
長崎大学の論文