T cell priming versus T cell tolerance induced by synthetic peptides.

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.

• Authors: P Aichele, K Brduscha-Riem, R M Zinkernagel, H Hengartner, H Pircher
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 182 Issue 1 Pg. 261-6 (Jul 01 1995) ISSN: 0022-1007 [Print] United States
• PMID: 7540654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, Viral
• Epitopes
• Glycoproteins
• Nucleoproteins
• Peptide Fragments
• Viral Proteins
• glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
• nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus
• nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus

Topics

• Adjuvants, Immunologic
• Animals
• Antigens, Viral (administration & dosage, chemistry, immunology)
• Epitopes (immunology)
• Glycoproteins (administration & dosage, immunology)
• Immune Tolerance
• Immunization
• Immunization Schedule
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Lymphocyte Activation
• Lymphocytic choriomeningitis virus (immunology)
• Mice
• Mice, Inbred C57BL
• Nucleoproteins (administration & dosage, immunology)
• Peptide Fragments (administration & dosage, chemical synthesis, immunology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Thymectomy
• Viral Proteins