Membranes activate tumor- and virus-specific precursor cytotoxic T lymphocytes in vivo and stimulate tumor-specific T lymphocytes in vitro: implications for vaccination.
Plasma membranes contain the entire antigenic repertoire of a cell in the form of processed antigens presented as peptides by major histocompatibility complex (MHC) class I molecules. We report here that plasma membranes but not internal membranes of cognate tumors stimulate murine fibrosarcoma and human melanoma-specific cytotoxic T lymphocyte (CTL) clones in vitro in an antigen-specific. MHC class I-restricted manner. Although stimulation of CTLs by class I-peptide complexes on reconstituted membranes has been documented before, this is the first demonstration of stimulation of cloned CTLs by natural, endogenously processed MHC class I-peptide complexes on plasma membranes. In addition to their ability to stimulate CTLs in vitro, immunization of syngeneic mice with membranes derived from ultraviolet-induced tumor cells, SV40 transformed fibroblasts, or influenza-infected fibroblasts elicits an antigen-specific, MHC class I restricted primary CTL response. To the best of our knowledge, this is also the first demonstration of the ability of cellular membranes to prime an MHC class I-restricted CTL responses in vivo. The ability of membranes to prime a CTL response in vivo suggests that they may be used as T-cell vaccines against tumors or infectious viruses. This approach circumvents the difficulties in generation of human tumor cell lines and identification of CTL-recognized determinants for vaccination and avoids some of the risks associated with whole-cell vaccination such as inoculation of patients with immunosuppressive factors, transforming DNA, or infectious viruses.
Department of Biological Sciences, Fordham University, Bronx, New York 10458.
M
M
Heike
N E
NE
Blachere
T
T
Wölfel
K H
KH
Meyer zum Büschenfelde
S
S
Störkel
P K
PK
Srivastava
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014780:Viruses / Q000276:immunology
D015395:Histocompatibility Antigens Class I