Route of uptake of palmitoylated encephalitogenic peptides of myelin proteolipid protein by antigen-presenting cells: importance of the type of bond between lipid chain and peptide and relevance to autoimmunity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Nadège A PfenderJudith M Greer

Abstract

Previously, we have shown that thiopalmitoylation of peptides of myelin proteolipid protein, as occurs naturally in vivo, increases their ability to induce experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, and skews the autoimmune response toward a CD4(+)-mediated response. In contrast, the same peptide, when synthesized with a stable amide bond between peptide and lipid, inhibits experimental autoimmune encephalomyelitis and skews the response toward a CD8(+) response. The aim of the current study was to determine the mechanisms responsible for these observations. We show that proteolipid protein lipopeptides, when synthesized with a thioester bond between the lipid and the peptide, are taken up into APCs via an actin-independent endocytic route, the thioester bond is cleaved in the endosome, and the peptide is subsequently displayed on the surface of the APC in the context of MHC class II. The same peptide, when synthesized with the lipid attached via a stable amide bond, rapidly enters into the cytoplasm of the APC and forms micelles; however, the bond between peptide and lipid is not cleaved, and the micelles travel via the endoplasmic reticulum to complex with MHC class I. These findings ha...Continue Reading

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Citations

Dec 7, 2013·Multiple Sclerosis International·Judith M Greer
May 12, 2016·Current Diabetes Reports·Rene J McLaughlinBart O Roep
Feb 4, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nancy C CloakeJudith M Greer
May 15, 2015·International Reviews of Immunology·Evan L SauerJudith M Greer
Sep 8, 2017·Expert Review of Vaccines·Mathieu SurenaudJean-Daniel Lelièvre
Feb 28, 2009·Biochemistry·Dimitris MissirlisMatthew Tirrell
Jan 18, 2015·Journal of Neuroimmunology·Susana BrunElisabeth Trifilieff

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