In vivo administration of major histocompatibility complex class I-specific peptides from influenza virus induces specific cytotoxic T cell hyporesponsiveness.
We have been investigating the immunogenicity of two class I major histocompatibility complex-specific peptides with a sequence derived from influenza virus nucleoprotein specific for Kd and one for Db. Peptide-modified splenocytes are unable to immunize for a primary cytotoxic T (Tc) cell response in vivo, or secondary response in vitro. Peptide-modified stimulator cells can boost virus-primed splenocytes for a strong secondary response in vitro. Animals primed with syngeneic peptide-modified splenocytes upon challenge with virus in vivo do not generate strong secondary Tc cell responses on day 3 after challenge in contrast to virus primed animals. Day 6 responses of virus-challenged, peptide-primed animals are reduced as compared to unprimed mice. This hyporesponsiveness is independent of CD8+ T cells in the priming population and can be elicited with tumor cell lines. The data are discussed in the framework of the two-signal model of immune induction.
Müllbacher
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Division of Cell Biology, John Curtin School of Medical Research Australian National University, Canberra City, ACT.
Tha Hla
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D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007108:Immune Tolerance; D007117:Immunization, Secondary; D016056:Immunodominant Epitopes / Q000235:genetics; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009842:Oligopeptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins