Thiopalmitoylation of altered peptide ligands enhances their protective effects in an animal model of multiple sclerosis

Cloake, Nancy C., Beaino, Wissam, Trifilieff, Elisabeth and Greer, Judith M. (2014) Thiopalmitoylation of altered peptide ligands enhances their protective effects in an animal model of multiple sclerosis. Journal of Immunology, 192 5: 2244-2251. doi:10.4049/jimmunol.1301871

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Author Cloake, Nancy C.
Beaino, Wissam
Trifilieff, Elisabeth
Greer, Judith M.
Title Thiopalmitoylation of altered peptide ligands enhances their protective effects in an animal model of multiple sclerosis
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2014-01-31
Year available 2014
Sub-type Article (original research)
DOI 10.4049/jimmunol.1301871
Open Access Status DOI
Volume 192
Issue 5
Start page 2244
End page 2251
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract Previously, we have shown that conjugation of a palmitic chain via a thioester bond to a cysteine residue in weakly or nonencephalitogenic or neuritogenic peptides markedly enhances their ability to induce autoimmune disease in an MHC class II–restricted manner. From those studies, however, it was not clear whether thiopalmitoylation of the peptides was merely enhancing their disease-inducing potential or whether the lipid was itself playing a pathogenic role. To investigate this further, we have now tested the effects of thiopalmitoylation on MHC class II–restricted altered peptide ligands (APLs), which are normally protective in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. We hypothesized that if thiopalmitoylation of a peptide merely enhances its innate potential, then thiopalmitoylated APLs (S-palmAPLs) should show enhanced protective effects. Alternatively, if thiopalmitoylation itself can make a peptide pathogenic, then S-palmAPLs should have decreased therapeutic potential. We synthesized APLs and corresponding S-palmAPLs and showed that the S-palmAPLs were much more effective than the nonconjugated APL at inhibiting the development of experimental autoimmune encephalomyelitis. This was due to several features of the S-palmAPL:S-palmAPL–primed cells show an enhanced ability to proliferate and produce the anti-inflammatory cytokine, IL-10, in vitro. Furthermore, the bioavailability of S-palmAPL was greatly enhanced, compared with the nonpalmitoylated APL, and S-palm APL was taken up more rapidly into dendritic cells and channeled into the MHC class II processing pathway. These results show that thiopalmitoylation of MHC class II–restricted peptides is a simple way to enhance their effects in vivo and could have wide therapeutic application.
Keyword Immunology
Immunology
IMMUNOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 05 Mar 2014, 02:24:34 EST by Judith M Greer on behalf of School of Medicine