{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T02:10:05Z","timestamp":1792375805943,"version":"4.4.0"},"posted":{"date-parts":[[2023,7,26]]},"group-title":"Immunology","reference-count":62,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Major histocompatibility complex (MHC) class II professional antigen presenting cell-na\u00efve CD4+ T cell interactions via the T-cell receptor complex are necessary for adaptive immunity. MHC class II upregulation in multiple cell types occurs in human autoimmune polyneuropathy patient biopsies, necessitating studies to ascertain cellular signaling pathways required for tissue-specific autoimmunity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Cryopreserved Guillain-Barr\u00e9 syndrome (GBS) patient sural nerve biopsies and sciatic nerves from the severe murine experimental autoimmune neuritis (sm-EAN) GBS model were studied. Cultured conditional ready MHC Class II antigen A-alpha chain (H2-Aa) embryonic stem cells were used to generate H2-Aa\n                    <jats:sup>flox\/+<\/jats:sup>\n                    C57BL\/6 mice. Mice were backcrossed and intercrossed to the SJL background to generate H2-Aa\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    SJL mice, bred with hemizygous Tamoxifen-inducible von Willebrand factor Cre recombinase (vWF-iCre\/+) SJL mice to generate H2-Aa\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ; vWF-iCre\/+ to study microvascular endothelial cell adaptive immune responses. Sm-EAN was induced in adult female SJL Tamoxifen-treated H2-Aa\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ; vWF-iCre\/+ mice and H2-Aa\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ; +\/+ littermate controls. Neurobehavioral, electrophysiological and histopathological assessments were performed at predefined time points.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Endoneurial endothelial cell MHC class II expression was observed in normal and inflamed human and mouse peripheral nerves. Adult female Tamoxifen-treated H2-Aa\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ; vWF-iCre\/+ did not develop sm-EAN despite extensive MHC class II expression in lymphoid and non-lymphoid tissues.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>\n                    A conditional MHC class II knockout mouse to study cell- and time-dependent adaptive immune responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    is developed. Initial studies show microvascular endothelial cell MHC class II expression is necessary for peripheral nerve specific autoimmunity, as advocated by human\n                    <jats:italic>in vitro<\/jats:italic>\n                    adaptive immunity and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    transplant rejection studies.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.07.24.550421","type":"posted-content","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T22:10:12Z","timestamp":1690409412000},"source":"Crossref","is-referenced-by-count":3,"title":["Development of a major histocompatibility complex class II conditional knockout mouse to study cell-specific and time-dependent adaptive immune responses in peripheral nerves"],"prefix":"10.64898","author":[{"given":"Eroboghene E.","family":"Ubogu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Conner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023072811550787000_2023.07.24.550421v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01907"},{"key":"2023072811550787000_2023.07.24.550421v1.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78088"},{"key":"2023072811550787000_2023.07.24.550421v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.10.012"},{"key":"2023072811550787000_2023.07.24.550421v1.4","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12929"},{"key":"2023072811550787000_2023.07.24.550421v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri2496"},{"issue":"8","key":"2023072811550787000_2023.07.24.550421v1.6","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nrneurol.2014.121","article-title":"Guillain-Barre syndrome: pathogenesis, diagnosis, treatment and prognosis","volume":"10","author":"van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA","year":"2014","journal-title":"Nature reviews Neurology"},{"key":"2023072811550787000_2023.07.24.550421v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00339-1"},{"issue":"11","key":"2023072811550787000_2023.07.24.550421v1.8","first-page":"3041","article-title":"Guillain-Barre syndrome in the 100 years since its description by Guillain","volume":"139","year":"2016","journal-title":"Barre and Strohl. Brain: a journal of neurology"},{"key":"2023072811550787000_2023.07.24.550421v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880150506"},{"key":"2023072811550787000_2023.07.24.550421v1.10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/ana.410090713","article-title":"Immunological characterization of sural nerve biopsies from patients with Guillain-Barre syndrome","volume":"9","year":"1981","journal-title":"Annals of neurology"},{"key":"2023072811550787000_2023.07.24.550421v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00328-7"},{"key":"2023072811550787000_2023.07.24.550421v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199604)19:4<474::AID-MUS8>3.0.CO;2-9"},{"key":"2023072811550787000_2023.07.24.550421v1.13","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1599-0"},{"key":"2023072811550787000_2023.07.24.550421v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1466-4"},{"key":"2023072811550787000_2023.07.24.550421v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156"},{"key":"2023072811550787000_2023.07.24.550421v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00067.x"},{"key":"2023072811550787000_2023.07.24.550421v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00117-0"},{"key":"2023072811550787000_2023.07.24.550421v1.18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130224"},{"key":"2023072811550787000_2023.07.24.550421v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.12.033"},{"key":"2023072811550787000_2023.07.24.550421v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.020"},{"key":"2023072811550787000_2023.07.24.550421v1.21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002835"},{"key":"2023072811550787000_2023.07.24.550421v1.22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.8386"},{"key":"2023072811550787000_2023.07.24.550421v1.23","doi-asserted-by":"crossref","unstructured":"Rothermel AL , Wang Y , Schechner J , Mook-Kanamori B , Aird WC , Pober JS , Tellides G , Johnson DR . Endothelial cells present antigens in vivo. BMC Immunol 2004;5:5.","DOI":"10.1186\/1471-2172-5-5"},{"key":"2023072811550787000_2023.07.24.550421v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052586"},{"key":"2023072811550787000_2023.07.24.550421v1.25","doi-asserted-by":"crossref","unstructured":"Lopes Pinheiro MA , Kamermans A , Garcia-Vallejo JJ , van Het Hof B , Wierts L , O\u2019Toole T , Boeve D , Verstege M , van der Pol SM , van Kooyk Y , de Vries HE , Unger WW . Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration. Elife 2016;5.","DOI":"10.7554\/eLife.13149"},{"key":"2023072811550787000_2023.07.24.550421v1.26","doi-asserted-by":"crossref","unstructured":"Manes TD , Wang V , Pober JS . Costimulators expressed on human endothelial cells modulate antigen-dependent recruitment of circulating T lymphocytes. Front Immunol 2022;13:1016361.","DOI":"10.3389\/fimmu.2022.1016361"},{"key":"2023072811550787000_2023.07.24.550421v1.27","doi-asserted-by":"crossref","unstructured":"Abrahimi P , Qin L , Chang WG , Bothwell AL , Tellides G , Saltzman WM , Pober JS . Blocking MHC class II on human endothelium mitigates acute rejection. JCI Insight 2016;1(1).","DOI":"10.1172\/jci.insight.85293"},{"key":"2023072811550787000_2023.07.24.550421v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.10.2020"},{"key":"2023072811550787000_2023.07.24.550421v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90070-1"},{"key":"2023072811550787000_2023.07.24.550421v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(91)90065-F"},{"issue":"1","key":"2023072811550787000_2023.07.24.550421v1.31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/glia.20903","article-title":"Expression of antigen processing and presenting molecules by Schwann cells in inflammatory neuropathies","volume":"58","year":"2010","journal-title":"Glia"},{"key":"2023072811550787000_2023.07.24.550421v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210404"},{"key":"2023072811550787000_2023.07.24.550421v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(86)90059-7"},{"key":"2023072811550787000_2023.07.24.550421v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.11.006"},{"issue":"1","key":"2023072811550787000_2023.07.24.550421v1.35","doi-asserted-by":"crossref","first-page":"12518","DOI":"10.1038\/s41598-017-12744-2","article-title":"Meyer Zu Horste G. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II","volume":"7","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"2023072811550787000_2023.07.24.550421v1.36","doi-asserted-by":"crossref","first-page":"17477","DOI":"10.1038\/s41598-017-17475-y","article-title":"The Human Blood-Nerve Barrier Transcriptome","volume":"7","year":"2017","journal-title":"Sci Rep"},{"key":"2023072811550787000_2023.07.24.550421v1.37","doi-asserted-by":"crossref","unstructured":"Gerber D , Pereira JA , Gerber J , Tan G , Dimitrieva S , Yanguez E , Suter U . Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve ATlas (SNAT). Elife 2021;10.","DOI":"10.7554\/eLife.58591"},{"key":"2023072811550787000_2023.07.24.550421v1.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403070"},{"key":"2023072811550787000_2023.07.24.550421v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20641"},{"key":"2023072811550787000_2023.07.24.550421v1.40","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.2.999"},{"key":"2023072811550787000_2023.07.24.550421v1.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4567"},{"key":"2023072811550787000_2023.07.24.550421v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20335"},{"key":"2023072811550787000_2023.07.24.550421v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"issue":"4","key":"2023072811550787000_2023.07.24.550421v1.44","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1538\/expanim.62.295","article-title":"Novel ROSA26 Cre-reporter knock-in C57BL\/6N mice exhibiting green emission before and red emission after Cre-mediated recombination","volume":"62","year":"2013","journal-title":"Exp Anim"},{"key":"2023072811550787000_2023.07.24.550421v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24085-9"},{"key":"2023072811550787000_2023.07.24.550421v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00249-6"},{"key":"2023072811550787000_2023.07.24.550421v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2009.11.019"},{"key":"2023072811550787000_2023.07.24.550421v1.48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01092.x"},{"key":"2023072811550787000_2023.07.24.550421v1.49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090463"},{"key":"2023072811550787000_2023.07.24.550421v1.50","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21588"},{"key":"2023072811550787000_2023.07.24.550421v1.51","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2018.1540904"},{"issue":"7","key":"2023072811550787000_2023.07.24.550421v1.52","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/PAI.0000000000000927","article-title":"A Simple and Quick Method for Decalcification Using Mouse Tail as a Model for Preparation of Lymphedema Study","volume":"29","year":"2021","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"2023072811550787000_2023.07.24.550421v1.53","doi-asserted-by":"publisher","DOI":"10.1007\/BF01463929"},{"issue":"2","key":"2023072811550787000_2023.07.24.550421v1.54","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/jns.12326","article-title":"In situ molecular characterization of endoneurial microvessels that form the blood-nerve barrier in normal human adult peripheral nerves","volume":"24","year":"2019","journal-title":"Journal of the peripheral nervous system: JPNS"},{"key":"2023072811550787000_2023.07.24.550421v1.55","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100171"},{"key":"2023072811550787000_2023.07.24.550421v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.010"},{"key":"2023072811550787000_2023.07.24.550421v1.57","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.1.117"},{"key":"2023072811550787000_2023.07.24.550421v1.58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00813.x"},{"key":"2023072811550787000_2023.07.24.550421v1.59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.3074"},{"key":"2023072811550787000_2023.07.24.550421v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2014.03.014"},{"issue":"7","key":"2023072811550787000_2023.07.24.550421v1.61","doi-asserted-by":"crossref","first-page":"e0131374","DOI":"10.1371\/journal.pone.0131374","article-title":"Human Leukocyte Antigen DQB1 (HLA-DQB1) Polymorphisms and the Risk for Guillain-Barre Syndrome: A Systematic Review and Meta-Analysis","volume":"10","year":"2015","journal-title":"PloS one"},{"issue":"9","key":"2023072811550787000_2023.07.24.550421v1.62","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1002\/acn3.50884","article-title":"Human leukocyte antigen-DQB1 polymorphisms and haplotype patterns in Guillain-Barre syndrome","volume":"6","year":"2019","journal-title":"Ann Clin Transl Neurol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.07.24.550421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:59:13Z","timestamp":1768453153000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.07.24.550421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,26]]},"references-count":62,"URL":"https:\/\/doi.org\/10.1101\/2023.07.24.550421","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1002\/mus.28193","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,7,26]]},"subtype":"preprint"}}