{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:03:07Z","timestamp":1790229787640,"version":"4.1.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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. Neurol."],"abstract":"<jats:p>\n                    Molecular mimicry is considered essential for peripheral nerve-specific autoimmunity: a process by which antibodies, systemically generated primarily as a consequence of infection with bacteria or viruses possessing epitopes that are similarly expressed by peripheral axon complex gangliosides or peripheral nerve myelin proteins, are hypothesized to induce peripheral nerve injury in genetically susceptible individuals. Human\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies have proposed that recently activated antigen-specific effector memory CD4+ T-cells initiate tissue specific autoimmunity by T-cell receptor-driven transmigration following local microvasculature activation. However, how do these rare T-cells find their way from secondary lymphoid organs where they are generated to restrictively migrate to peripheral nerves and nerve roots to initiate an autoimmune response? Using severe murine experimental autoimmune neuritis as an animal model of peripheral nerve-specific autoimmunity, we elucidated that Major Histocompatibility Complex (MHC) class II expression on endoneurial endothelial cells is essential for disease onset using conditional knockout transgenic mice. This implies that specific BNB antigen-expressing MHC Class II molecules could serve as a directional cue for antigen-specific effector memory CD4+ T-cell transmigration: an active, molecular-dependent, coordinated multi-step mechanistic paradigm, to initiate tissue-specific autoimmunity and drive subsequent monocyte and B-cell infiltration, resulting in peripheral nerve demyelination and axonal degeneration. Based on these initial observations, I propose to redefine molecular mimicry as follows: The process by which recently activated antigen-specific effector memory CD4+ T-cells engage with MHC class II-expressing microvascular endothelial cells that present the same processed antigen peptide sequences during immunosurveillance to trigger their transmigration and initiate tissue-specific autoimmunity.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1968458","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:43:46Z","timestamp":1790228626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mammalian peripheral nerve specific autoimmunity: proposed mechanisms and redefinition of molecular mimicry"],"prefix":"10.3389","volume":"17","author":[{"given":"Eroboghene E.","family":"Ubogu","sequence":"first","affiliation":[{"name":"Division of Neuromuscular Disease, Department of Neurology, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/joim.12395","article-title":"Human autoimmune diseases: a comprehensive update","volume":"278","author":"Wang","year":"2015","journal-title":"J Intern Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"102266","DOI":"10.1016\/j.coi.2022.102266","article-title":"The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention","volume":"80","author":"Miller","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1080\/21645515.2018.1493415","article-title":"Immunotherapy of Guillain-Barre 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