{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:35Z","timestamp":1782276575989,"version":"3.54.5"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"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                    Neurons upregulate major histocompatibility complex class I (MHC I) during demyelination, enabling the presentation of self-antigens to cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. While this phenomenon is well described in multiple sclerosis lesions, its functional significance for disease progression remains poorly understood. Here, we test the hypothesis that neuronal MHC I expression promotes CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated neurodegeneration in demyelinating disease. Using genetic and viral approaches to selectively ablate\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2082-microglobulin (\u03b2\u2082M) in neurons, we demonstrate that the loss of neuronal MHC I limits antigen presentation, attenuates the activation of neuron-antigen\u2013specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and reduces the recruitment of these cells to the demyelinated central nervous system (CNS). In myelin oligodendrocyte glycoprotein (MOG\u2083\u2085\u2013\u2085\u2085)-induced experimental autoimmune encephalomyelitis, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell ablation during active disease limited neuronal injury and improved clinical recovery. Similarly, neuronal\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2082M ablation decreased clinical disease burden without affecting CNS T cell infiltration. Likewise, in the context of cuprizone intoxication, neuronal\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2082M deletion reduced peripheral activation and CNS recruitment of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells recognizing a neuron-restricted neoantigen. It protected neoantigen-expressing neurons from cognate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated cytotoxicity. Collectively, these findings identify neuronal MHC I\u2013dependent antigen presentation as a driver of both the immune surveillance of neuronal antigens and neuronal injury during demyelination.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1813496","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:43:23Z","timestamp":1782276203000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal expression of \u03b22M and MHC I are essential for peripheral surveillance and targeting of neuron-restricted antigens"],"prefix":"10.3389","volume":"17","author":[{"given":"Benjamin D. S.","family":"Clarkson","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic","place":["Rochester, MN, United States"]},{"name":"Department of Neurology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie E.","family":"Schille","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy J. Z.","family":"Garland","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Westphal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles L.","family":"Howe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic","place":["Rochester, MN, United States"]},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic","place":["Rochester, MN, United States"]},{"name":"Division of Experimental Neurology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1093\/brain\/aww032","article-title":"In situ expansion of T cells that recognize distinct self-antigens sustains autoimmunity in the CNS","volume":"139","author":"Ramadan","year":"2016","journal-title":"Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/1742-2094-10-118","article-title":"Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis","volume":"10","author":"Puentes","year":"2013","journal-title":"J Neuroinflammation"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1084\/jem.20122143","article-title":"Neuroprotective intervention by interferon-gamma blockade prevents CD8+ T cell-mediated dendrite and synapse 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