Table 1.

Biological effects of myelin-derived peptides (linear, cyclic, mannan conjugated).

Peptide Analog [Reference]	Major Effects
MBP83–99 and PLP139–151 [10,11,12,13,14,15,16,17,18]	These agonist peptides are involved in the pathophysiology of MS and also induce EAE in animal models.
MBP82–98 [40,41]	Dirucotide in animal models inhibits disease and in early human clinical trials showed efficacy; however, the peptide did not meet primary endpoints in phase III-trials.
cyclic(87–99)[MBP87–99] [23]	Stimulates Th2 cytokines and inhibits EAE in mice.
MBP87–99(R91,A96), MBP87–99(A91,A96) [21]	Induces IL-4 and antagonizes IFNγ responses in mice.
MBP72–85 [22]	These agonist peptides induce EAE in mice and Th1 responses in humans.
MBP72–85(A79) [22]	Suppresses EAE in mice.
PLP139–151(L144, R147) [42]	Antagonizes PLP-specific T-clones in vitro.
cyclic-MBP82–98	Exerts strong binding to the HLA-DR2 and lowers binding to the HLA-DR4 allele in vitro
cyclic-MBP87–99(A96) or (R91A96) [21,30]	Suppresses proliferation of CD4+ T cells and exerts IL-10 selectivity in vitro. Binds to HLA-DR4 and is stable to lysosomal enzymes and cathepsins B, D, and H.
cyclic-MOG35–55 [44] cyclic-PLP131–151 [42] linear and cyclic-MBP83–99(A91,A96) [27] Mannan-linear and cyclic-MBP83–99(A91,A96) [27]	Reduces EAE, demyelination, and chronic axonopathy in acute and chronic phases of EAE in mice. Low disease burden in regards to EAE in mice with minimal inflammatory, demyelinating, and axonopathic pathology compared to its linear counterpart. Decreases IFNγ responses in mice. Diverts the “bad” IFNγ to “good” IL-4 cytokine in mice.
Mannan-MOG35–55 [28]	Protects mice against EAE in prophylactic and therapeutic protocols, with oxidized-conjugated peptides giving the best results.
Cyclo(87–99)MBP87-99(A91,A96) [27,30] Mannan-cyclo(87–99)MBP87-99(A91,A96) [27,30]	Decreases Th1 responses. Shifts Th1 responses to Th2 responses.
MBP87–99[Cit91,A96,Cit97] [25] cyclic-MBP87–99[Cit91,A96,Cit97] [25]	Induces T-cell proliferation and IFNγ secretion in mice. Activates T cells and increases IFNγ secretion in mice.