Induction of primary, human antigen-specific cytotoxic T lymphocytes in vitro using dendritic cells pulsed with peptides

摘要: Using a murine metastasis model, we have previously shown that antigen-presenting cells (APC) loaded with unfractionated peptides derived from poorly immunogenic, highly metastatic tumor represent potent form of vaccine. The antimetastatic effect peptide pulsed APC could be further enhanced by pretreating the antisense oligonucleotides directed against TAP-2 gene to increase density specific peptide-major histocompatibility complex (MHC) class I complexes and thereby improve function treated (Nair SK et al., J Immunol 1996;156:1772). In this study, investigated whether similar strategies can used enhance potency human dendritic (DC) present antigen. We show DC encoding known cytotoxic T-lymphocyte (CTL) epitopes stimulate both memory primary CTL responses in vitro after two cycles stimulation peptide-pulsed DC. Two approaches were peptide-MHC on surface One approach was inhibit transporter associated antigen presentation (TAP) using TAP oligonucleotides. second endogenous generation proteasome inhibitor. Treatment either or inhibitor resulted dramatic enhancement induction.