Herpes simplex virus class I-restricted peptide induces cytotoxic T lymphocytes in vivo independent of CD4+ T cells.
Cytotoxic T cells were induced in vivo by immunizing C57BL/6 mice with a single dose of a short synthetic peptide representing amino acid residues 497-507 from HSV-1 glycoprotein B. Primed lymph node cells did not require in vitro boosting with peptide and APC for CTL detection. The CTL were CD8+ and H-2b restricted. They were capable of lysing target cells exogenously sensitized with peptide or endogenously processed glycoprotein B. Virus-primed CTL produced an anamnestic response in vivo upon peptide challenge, indicating that peptide-specific CTL may be relevant to infection. The requirement of CD4+ T cells for CD8+ CTL activation was investigated by depleting CD4+ cells in vivo with GK1.5 mAb. CD4+ T cell depletion did not abrogate CTL generation. These results suggest that glycoprotein B peptide 497-507 activates CD8+ CTL in vivo in a manner independent of CD4+ T cells. This is the first study in which a class I-restricted peptide derived from a HSV protein was used to activate CTL in vivo, and in which a synthetic peptide was shown to activate CTL independent of CD4+ T cell help. Our data are relevant to viral vaccine development and to processing and presentation of viral epitopes.
Vasilakos
J P
JP
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, OH 45267-0524.
Michael
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007117:Immunization, Secondary; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D016827:CD8 Antigens; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus