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.
Langlade-Demoyen
P
P
INSERM U277, Département d'Immunologie, Institut Pasteur, Paris, France.
Levraud
J P
JP
Kourilsky
P
P
Abastado
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D006183:H-2 Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D010455:Peptides