Abstract
Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.
Keywords:
Type 1 diabetes; atherosclerosis; insulinoma antigen-2; peptide P277.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Atherosclerosis / chemically induced
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Blood Glucose / drug effects
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Blood Glucose / metabolism
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Cell Proliferation / drug effects
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Cells, Cultured
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Chaperonin 60 / administration & dosage
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Chaperonin 60 / pharmacology*
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Chaperonin 60 / toxicity
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Cytokines / metabolism
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / immunology
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Diabetes Mellitus, Type 1 / blood
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Diabetes Mellitus, Type 1 / chemically induced
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Diabetes Mellitus, Type 1 / drug therapy*
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Diabetes Mellitus, Type 1 / immunology
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Drug Design*
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Hypoglycemic Agents / administration & dosage
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Hypoglycemic Agents / pharmacology*
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Hypoglycemic Agents / toxicity
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Immunization
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Lymphocyte Activation / drug effects
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Male
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Mice, Inbred C57BL
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology*
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Peptide Fragments / toxicity
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Rabbits
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / administration & dosage
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / pharmacology*
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Receptor-Like Protein Tyrosine Phosphatases, Class 8 / toxicity
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / pharmacology*
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Recombinant Fusion Proteins / toxicity
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Streptozocin
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Time Factors
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Vaccines / administration & dosage
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Vaccines / pharmacology*
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Vaccines / toxicity
Substances
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Blood Glucose
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Chaperonin 60
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Cytokines
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Hypoglycemic Agents
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IA-2-P2 peptide
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Peptide Fragments
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Recombinant Fusion Proteins
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Vaccines
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peptide 277, heat shock protein 60
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Streptozocin
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Receptor-Like Protein Tyrosine Phosphatases, Class 8