{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:03Z","timestamp":1785417363346,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,11]]},"group-title":"Immunology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["K08AI187711"],"award-info":[{"award-number":["K08AI187711"]}]},{"award":["RM1NS138808"],"award-info":[{"award-number":["RM1NS138808"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Mental Health","award":["R01MH122471"],"award-info":[{"award-number":["R01MH122471"]}]},{"award":["K08NS126573"],"award-info":[{"award-number":["K08NS126573"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K08AI174061"],"award-info":[{"award-number":["K08AI174061"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,11]]},"abstract":"<jats:p>Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin\/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.<\/jats:p>","DOI":"10.64898\/2026.05.06.722823","type":"posted-content","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:40:16Z","timestamp":1778521216000},"source":"Crossref","is-referenced-by-count":0,"title":["AEGIS reveals epitope- and clone-resolved convergence of CNS B and T cell autoreactivity in ROHHAD"],"prefix":"10.64898","author":[{"given":"Aaron","family":"Bodansky","sequence":"first","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vida","family":"Ahyong","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Dayao","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Asaki","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShiLu","family":"Vanasupa","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Dandekar","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shini","family":"Chen","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Sabatino","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Klauer","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"Knudsen","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lizama Valenzuela","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"McCutcheon","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Zorn","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhman","family":"Sidhu","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yu","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Garcia","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Quandt","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Castillo Rojas","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Tilton","sequence":"additional","affiliation":[{"name":"University of California San Francisco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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