Abstract
It is well known that synthetic peptides are able to both induce and tolerize T cells. We have examined the parameters leading either to priming or tolerance of CD8+ cytotoxic T lymphocytes (CTL) in vivo with a major histocompatibility complex class I (H-2 Db) binding peptide derived from the glycoprotein (GP aa33-41) of lymphocytic choriomeningitis virus (LCMV). By varying dose, route, and frequency of LCMV GP peptide application, we found that a single local subcutaneous injection of 50-500 micrograms peptide emulsified in incomplete Freund's adjuvant protected mice against LCMV infection, whereas repetitive and systemic intraperitoneal application of the same dose caused tolerance of LCMV-specific CTL. The peptide-induced tolerance was transient in euthymic mice but permanent in thymectomized mice. These findings are relevant for a selective use of peptides as a therapeutic approach: peptide-induced priming of T cells for vaccination and peptide-mediated T cell tolerance for intervention in immunopathologies and autoimmune diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic
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Animals
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Antigens, Viral / administration & dosage
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Antigens, Viral / chemistry
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Antigens, Viral / immunology*
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Epitopes / immunology
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Glycoproteins / administration & dosage
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Glycoproteins / immunology*
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Immune Tolerance*
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Immunization
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Immunization Schedule
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Injections, Intraperitoneal
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Injections, Subcutaneous
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Lymphocyte Activation*
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Lymphocytic choriomeningitis virus / immunology
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Mice
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Mice, Inbred C57BL
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Nucleoproteins / administration & dosage
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Nucleoproteins / immunology*
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Peptide Fragments / administration & dosage
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Peptide Fragments / chemical synthesis
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Peptide Fragments / immunology*
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T-Lymphocytes, Cytotoxic / drug effects*
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T-Lymphocytes, Cytotoxic / immunology
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Thymectomy
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Viral Proteins*
Substances
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Adjuvants, Immunologic
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Antigens, Viral
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Epitopes
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Glycoproteins
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Nucleoproteins
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Peptide Fragments
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus
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nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus