1. Cyclization of PLP 139-151 peptide reduces its encephalitogenic potential in experimental autoimmune encephalomyelitis.
- Author
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Lourbopoulos A, Matsoukas MT, Katsara M, Deraos G, Giannakopoulou A, Lagoudaki R, Grigoriadis N, Matsoukas J, and Apostolopoulos V
- Subjects
- Amino Acid Sequence, Animals, Cyclization, Encephalomyelitis, Autoimmune, Experimental chemically induced, Encephalomyelitis, Autoimmune, Experimental pathology, Epitopes adverse effects, Epitopes chemistry, Epitopes immunology, Epitopes metabolism, Female, Histocompatibility Antigens Class II chemistry, Histocompatibility Antigens Class II immunology, Histocompatibility Antigens Class II metabolism, Inflammation chemically induced, Inflammation immunology, Inflammation pathology, Mice, Inbred Strains, Molecular Docking Simulation, Myelin Proteolipid Protein adverse effects, Myelin Proteolipid Protein chemistry, Myelin Proteolipid Protein metabolism, Peptide Fragments adverse effects, Peptide Fragments chemistry, Peptide Fragments metabolism, Peptides, Cyclic adverse effects, Peptides, Cyclic chemical synthesis, Peptides, Cyclic metabolism, Protein Binding, Protein Conformation, Receptors, Antigen, T-Cell chemistry, Receptors, Antigen, T-Cell immunology, Spinal Cord pathology, T-Lymphocytes metabolism, Encephalomyelitis, Autoimmune, Experimental immunology, Myelin Proteolipid Protein immunology, Peptide Fragments immunology, Peptides, Cyclic immunology
- Abstract
We report the novel synthesis of cyclic PLP
139-151 (cPLP) and its application in SJL/J mice to study its encephalitogenic effects. Our results indicate that the cPLP analog is minimally encephalitogenic when administered to induce experimental autoimmune encephalomyelitis (low disease burden, minimal inflammatory, demyelinating and axonopathic pathology compared to its linear counterpart). Proliferation assays confirmed the low stimulatory potential of the cPLP compared to linPLP (2.5-fold lower proliferation) as well as inducing lower antibody responses. Molecular modeling showed a completely different TCR recognition profile of cPLP in regard to linPLP, where H147 replaces W144 and F151 -K150 replace H147 as TCR contacts, which may explain the difference on each peptide's response., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2018
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