{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:35:03Z","timestamp":1777354503412,"version":"3.51.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by autoreactive T-cell responses against myelin antigens. Current disease-modifying therapies (DMTs) broadly suppress immune activity but do not restore antigen-specific immune tolerance and may cause significant adverse effects. Antigen-specific immunotherapies offer a rational alternative aimed at selectively re-educating the immune system without compromising protective immunity. Structural determinants of myelin antigens, including arginine-dependent conformational stability and post-translational modifications such as citrullination, critically influence their immunogenic and tolerogenic properties. Recent advances highlight the potential of oxidized mannan-conjugated myelin oligodendrocyte glycoprotein peptide (OM-MOG35-55) to modulate antigen-specific immune responses in experimental models and human immune cells. Studies suggest that OM-MOG35-55 can influence dendritic cell (DC)-mediated antigen presentation and favor the expansion of CD4+PD-1+ and CD4+CD25+Foxp3+ T-cell populations and the production of regulatory cytokines such as IL-10 and TGF-\u03b21. When combined with vitamin D3 conditioning of DCs, the immunomodulatory potential of OM-MOG35-55 appears enhanced. Nevertheless, the precise mechanisms underlying OM-MOG-mediated immune modulation are not fully defined, and the antigenic heterogeneity of MS and the limited predictive value of EAE models highlight the need for cautious interpretation of preclinical findings. This mini-review integrates structural, immunological, and translational evidence supporting OM-MOG35-55 as a promising platform for antigen-specific immunotherapeutic design and proposes a roadmap toward clinical validation of this immunotherapeutic strategy for MS.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1809907","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:32:35Z","timestamp":1777350755000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidized mannan-MOG35-55 conjugate as a platform for antigen-specific immune modulation in multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Athanasia","family":"Mouzaki","sequence":"first","affiliation":[{"name":"Laboratory of Immunohematology, Division of Hematology, Medical School, University of Patras","place":["Patras, Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Lise","family":"de Lastic","sequence":"additional","affiliation":[{"name":"Laboratory of Immunohematology, Division of Hematology, Medical School, University of Patras","place":["Patras, Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasso","family":"Apostolopoulos","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, RMIT University","place":["Melbourne, VIC, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Matsoukas","sequence":"additional","affiliation":[{"name":"NewDrug, P.C., Patras Science Park","place":["Patras, Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103480","article-title":"Current knowledge on multiple sclerosis pathophysiology, disability progression assessment and treatment options, and the role of autologous hematopoietic stem cell transplantation","volume":"23","author":"Gakis","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B2","article-title":"Myelin antigens and antimyelin antibodies","volume-title":"Advances in clinical immunology, medical microbiology, COVID-19, and big data 2021, chapter 5","author":"Seil","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17091398","article-title":"Regulatory cell populations in relapsing-remitting multiple sclerosis (RRMS) patients: Effect of disease activity and treatment regimens","volume":"17","author":"Rodi","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/s41392-025-02415-4","article-title":"Multiple sclerosis: molecular pathogenesis and therapeutic intervention","volume":"10","author":"Boutitah-Benyaich","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0320814","article-title":"Safety and efficacy of antigen-specific therapeutic approaches for multiple sclerosis: Systematic review","volume":"20","author":"\u00d6zt\u00fcrk","year":"2025","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/80525","article-title":"Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. 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