Abstract | BACKGROUND: AIM: The aim was to synthesize and test the immunological activity and cyclic analogs of PLP139-151 peptide and determine the immunological differences between adjuvant and conjugation to mannan. Materials & methods: We designed and synthesized cyclic peptides based on the linear PLP139-151 epitope by mutating critical T-cell receptor contact sites of residues W(144) and H(147), resulting in the mutant peptides PLP139-151, [L(144), R(147)]PLP139-151 or cyclo(139-151)PLP139-151 and cyclo(139-151) [L(144), R(147)]PLP139-151. In this study, mice were immunized with mutant peptides either emulsified in complete Freund's adjuvant or conjugated to reduced mannan and responses were assessed. RESULTS: Linear double-mutant peptide [L(144), R(147)]PLP139-151 induced high levels of IL-4 responses and low levels of IgG total, and cyclization of this analog elicited low levels of IFN-γ. Moreover, linear [L(144), R(147)]PLP139-151 conjugated to reduced mannan did not induce IFN-γ, whilst both linear agonist PLP139-151 and cyclic agonist cyclo(139-151)PLP139-151 induced IFN-γ-secreting T cells. Molecular dynamics simulations of linear and cyclic(139-151)PLP139-151 analogs indicated the difference in topology of the most important for biological activity amino acids. CONCLUSION:
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Authors | Maria Katsara, Spyros Deraos, Theodore V Tselios, Geoffrey Pietersz, John Matsoukas, Vasso Apostolopoulos |
Journal | Immunotherapy
(Immunotherapy)
Vol. 6
Issue 6
Pg. 709-24
( 2014)
ISSN: 1750-7448 [Electronic] England |
PMID | 25186603
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Epitopes
- Immunoglobulin G
- Mannans
- Myelin Proteolipid Protein
- Peptide Fragments
- Peptides
- Peptides, Cyclic
- myelin proteolipid protein (139-151)
- Interleukin-4
- Interferon-gamma
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Topics |
- Amino Acid Sequence
- Animals
- Encephalomyelitis, Autoimmune, Experimental
(immunology)
- Enzyme-Linked Immunosorbent Assay
- Epitopes
(chemistry, genetics, immunology)
- Female
- Humans
- Immunity, Cellular
(drug effects, immunology)
- Immunization
- Immunoglobulin G
(blood, immunology)
- Interferon-gamma
(immunology, metabolism)
- Interleukin-4
(immunology, metabolism)
- Mannans
(chemistry, immunology)
- Mice, Inbred Strains
- Multiple Sclerosis
(immunology)
- Mutation
(immunology)
- Myelin Proteolipid Protein
(genetics, immunology)
- Peptide Fragments
(genetics, immunology)
- Peptides
(chemistry, genetics, immunology, pharmacology)
- Peptides, Cyclic
(chemistry, genetics, immunology, pharmacology)
- T-Lymphocytes
(drug effects, immunology, metabolism)
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