Primary cytotoxic T lymphocyte induction using peptide-stripped autologous cells.

MHC class I molecules bind short peptides derived from endogenously synthesized 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 upon a brief and mild acid treatment without affecting cell viability or capacity of the peptide-stripped MHC molecules to re-bind exogenous peptides. Mouse or human blasts that have been peptide-stripped and reloaded with an exogenous peptide can induce in vitro peptide specific primary cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures. Mice immunized with syngeneic blasts that have been peptide-stripped and reloaded with a peptide derived from a tumor-associated antigen are protected against a subsequent challenge with a lethal dose of tumor cells. 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.