{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:49:57Z","timestamp":1787064597668,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MA6957\/1-1"],"award-info":[{"award-number":["MA6957\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Subgroups of autoantibodies directed against voltage-gated potassium channel (K\n                      <jats:sub>v<\/jats:sub>\n                      ) complex components have been associated with immunotherapy-responsive clinical syndromes. The high prevalence and the role of autoantibodies directly binding K\n                      <jats:sub>v<\/jats:sub>\n                      remain, however, controversial. Our objective was to determine K\n                      <jats:sub>v<\/jats:sub>\n                      autoantibody binding requirements and to clarify their contribution to the observed immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Binding epitopes were studied in sera (n = 36) and cerebrospinal fluid (CSF) (n = 12) from a patient cohort positive for K\n                      <jats:sub>v<\/jats:sub>\n                      1.2 but negative for 32 common neurological autoantigens and controls (sera n = 18 and CSF n = 5) by phospho and deep mutational scans. Autoantibody specificity and contribution to the observed immune response were resolved on recombinant cells, cerebellum slices, and nerve fibers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      83% of the patients (30\/36) within the studied cohort shared one out of the two major binding epitopes with K\n                      <jats:sub>v<\/jats:sub>\n                      1.2-3 reactivity. Eleven percent (4\/36) of the serum samples showed no binding. Fingerprinting resolved close to identical sequence requirements for both shared epitopes. K\n                      <jats:sub>v<\/jats:sub>\n                      autoantibody response is directed against juxtaparanodal regions in peripheral nerves and the axon initial segment in central nervous system neurons and exclusively mediated by the shared epitopes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Systematic mapping revealed two shared autoimmune responses, with one dominant K\n                      <jats:sub>v<\/jats:sub>\n                      1.2-3 autoantibody epitope being unexpectedly prevalent. The conservation of the molecular binding requirements among these patients indicates a uniform autoantibody repertoire with monospecific reactivity. The enhanced sensitivity of the epitope-based (10\/12) compared with that of the cell-based detection (7\/12) highlights its use for detection. The determined immunodominant epitope is also the primary immune response visible in tissue, suggesting a diagnostic significance and a specific value for routine screening.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1329013","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T01:05:13Z","timestamp":1712797513000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular dissection of an immunodominant epitope in Kv1.2-exclusive autoimmunity"],"prefix":"10.3389","volume":"15","author":[{"given":"Ivan","family":"Talucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike A.","family":"Arlt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai 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