PRIMARY CYTOTOXIC T-LYMPHOCYTE INDUCTION USING PEPTIDE-STRIPPED AUTOLOGOUS CELLS

MHC class I molecules bind short peptides derived from endogenously sy nthesized proteins. This binding occurs at neutral pH and MHC class I- peptide complexes dissociate at low or high pH. Here we show that MHC class I-peptide complexes expressed at the cell surface dissociate upo n a brief and mild acid treatment without affecting cell viability or capacity of the peptide-stripped MHC molecules to re-bind exogenous pe ptides. Mouse or human blasts that have been peptide-stripped and relo aded with an exogenous peptide can induce in vitro peptide specific pr imary cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures. Mice immunized with syngeneic blasts that have been peptide-stripped and r eloaded with a peptide derived from a tumor-associated antigen are pro tected against a subsequent challenge with a lethal dose of tumor cell s. The importance of these findings for viral and tumor immunotherapy as well as for unravelling the mechanisms of induction of primary CTL responses are discussed.