Cationic lipids direct a viral glycoprotein into the class I major histocompatibility complex antigen-presentation pathway.
Recombinant glycoprotein B (gB) of herpes simplex virus (HSV) was processed and presented by class I major histocompatibility complex (MHC) molecules after delivery into cells by using N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTAP), a commercially available cationic lipid used for DNA transfection. Cells treated with DOTAP-associated gB were susceptible to lysis by class I MHC-restricted, HSV-specific cytotoxic T lymphocytes (CTL), and the treated cells restimulated memory gB-specific CTL activity in spleen cells from HSV-infected mice. gB-specific CTL responses were detected in mice immunized with recombinant gB and DOTAP but not in those receiving gB emulsified in complete Freund's adjuvant. Thus, cationic lipids may facilitate induction of CD8+ T-cell responses in vaccinations with recombinant antigens, and they may serve as readily available reagents for dissecting class I MHC immunity to viruses and other intracellular pathogens.
Walker
C
C
Chiron Corporation, Emeryville, CA 94608.
Selby
M
M
Erickson
A
A
Cataldo
D
D
Valensi
J P
JP
Van Nest
G V
GV
D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; D005229:Fatty Acids, Monounsaturated; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D000644:Quaternary Ammonium Compounds; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane