{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:51:45Z","timestamp":1790373105933,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Shared VH1-46 gene usage has been described in B cells reacting to desmoglein 3 (Dsg3) in the autoimmune disease pemphigus vulgaris (PV), as well as B cells responding to rotavirus capsid protein VP6. In both diseases, VH1-46 B cells bearing few to no somatic mutations can recognize the disease Ag. This intriguing connection between an autoimmune response to self-antigen and an immune response to foreign Ag prompted us to investigate whether VH1-46 B cells may be predisposed to Dsg3-VP6 cross-reactivity. Focused testing of VH1-46 mAbs previously isolated from PV and rotavirus-exposed individuals indicates that cross-reactivity is rare, found in only one of seven VH1-46 IgG clonotypes. High-throughput screening of IgG B cell repertoires from two PV patients identified no additional cross-reactive clonotypes. Screening of IgM B cell repertoires from one non-PV and three PV patients identified specific cross-reactive Abs in one PV patient, but notably all six cross-reactive clonotypes used VH1-46. Site-directed mutagenesis studies indicate that amino acid residues predisposing VH1-46 Abs to Dsg3 reactivity reside in CDR2. However, somatic mutations only rarely promote Dsg3-VP6 cross-reactivity; most mutations abolish VP6 and\/or Dsg3 reactivity. Nevertheless, functional testing identified two cross-reactive VH1-46 Abs that both disrupt keratinocyte adhesion and inhibit rotavirus replication, indicating the potential for VH1-46 Abs to have both pathologic autoimmune and protective immune functions. Taken together, these studies suggest that certain VH1-46 B cell populations may be predisposed to Dsg3-VP6 cross-reactivity, but multiple mechanisms prevent the onset of autoimmunity after rotavirus exposure.<\/jats:p>","DOI":"10.4049\/jimmunol.1600567","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T02:34:49Z","timestamp":1468290889000},"page":"1065-1073","source":"Crossref","is-referenced-by-count":26,"title":["Determinants of VH1-46 Cross-Reactivity to Pemphigus Vulgaris Autoantigen Desmoglein 3 and Rotavirus Antigen VP6"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4628-303X","authenticated-orcid":false,"given":"Michael Jeffrey","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph T","family":"Ellebrecht","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-2415","authenticated-orcid":false,"given":"Christoph M","family":"Hammers","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-1757","authenticated-orcid":false,"given":"Gopal","family":"Sapparapu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University Medical Center , Nashville, TN 37232"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal E","family":"Boudreaux","sequence":"additional","affiliation":[{"name":"Virginia Tech Carilion School of Medicine and Research Institute , Roanoke, VA 24016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"McDonald","sequence":"additional","affiliation":[{"name":"Virginia Tech Carilion School of Medicine and Research Institute , Roanoke, VA 24016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0049-1079","authenticated-orcid":false,"suffix":"Jr.","given":"James E","family":"Crowe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University Medical Center , Nashville, TN 37232"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-7918","authenticated-orcid":false,"given":"Aimee S","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,15]]},"reference":[{"key":"2025030617474505200_r1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0022-5193(79)90275-3","article-title":"Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination","volume":"81","author":"Perelson","year":"1979","journal-title":"J. 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