Generation of human tumor-reactive cytotoxic T cells against peptides presented by non-self HLA class I molecules

摘要: The cyclin-D1 protein, which was found to be overexpressed in various human tumors, promotes cell cycle progression from the G1 into S phase. It is normally expressed at low levels several tissues and likely induce immunological tolerance. We have recently shown a murine system that T tolerance widely protein circumvented by raising cytotoxic lymphocytes (CTL) MHC-mismatched donors. In this study, we tested whether it possible raise allo-restricted CTL against protein. line T2 deficient genes encoding transporter associated with antigen processing (TAP), resulting inefficient loading of HLA-A2 class I molecules endogenous peptides. Thus, large number A2 can bind exogenously supplied synthetic Peripheral blood mononuclear cells HLA-A2-negative donors were stimulated presenting cyclin-D1-derived Cloning bulk cultures revealed proportion clones peptide specific. One induced lysed cyclin-D1-expressing breast cancer cells, but not control Epstein-Barr virus-transformed B lymphoid cells. results show used isolate tumor-reactive specific for peptides presented molecules.