{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:33:15Z","timestamp":1770287595847,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"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":[[2006,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The 77C\u2192G mutation in exon A of the human CD45 gene occurs with low frequency in healthy individuals. An enhanced frequency of 77C\u2192G individuals has been reported in cohorts of patients suffering from multiple sclerosis, systemic sclerosis, autoimmune hepatitis, and HIV-1. To investigate the mechanisms by which the variant allele may contribute to disease susceptibility, we compared T cell reactivity in heterozygous carriers of the mutation (healthy individuals and multiple sclerosis patients) and wild-type controls. In vitro-generated T cell lines and freshly isolated CD4+CD45R0+ primed\/memory T cells from 77C\u2192G individuals aberrantly expressed CD45RA isoforms and showed enhanced proliferation and IL-2 production when stimulated with anti-TCR\/CD3 mAb or Ag. Mutant T cell lines contained a more active pool of p56lck tyrosine kinase and responded with increased phosphorylation of Zap70 and TCR-\u03b6 and an enhanced Ca2+ flux to TCR\/CD3 stimulation. These data suggest that 77C\u2192G may act as a risk factor for certain diseases by increasing the intensity of TCR signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.176.2.931","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:43:16Z","timestamp":1398022996000},"page":"931-938","source":"Crossref","is-referenced-by-count":30,"title":["The 77C\u2192G Mutation in the Human CD45 (\n                    <i>PTPRC<\/i>\n                    ) Gene Leads to Increased Intensity of TCR Signaling in T Cell Lines from Healthy Individuals and Patients with Multiple Sclerosis"],"prefix":"10.1093","volume":"176","author":[{"given":"Hue-Tran","family":"Do","sequence":"first","affiliation":[{"name":"Transplantationslabor, Klinik fu\u0308r Viszeral-und Transplantationschirurgie , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Baars","sequence":"additional","affiliation":[{"name":"Transplantationslabor, Klinik fu\u0308r Viszeral-und Transplantationschirurgie , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Borns","sequence":"additional","affiliation":[{"name":"Transplantationslabor, Klinik fu\u0308r Viszeral-und Transplantationschirurgie , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Windhagen","sequence":"additional","affiliation":[{"name":"Neurologie, Medizinische Hochschule , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhard","family":"Schwinzer","sequence":"additional","affiliation":[{"name":"Transplantationslabor, Klinik fu\u0308r Viszeral-und Transplantationschirurgie , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,1,15]]},"reference":[{"key":"2026020211321978400_R1","first-page":"107","volume-title":"Annu. Rev. Immunol.","year":"2003"},{"key":"2026020211321978400_R2","first-page":"1548","volume-title":"J. Exp. Med.","year":"1987"},{"key":"2026020211321978400_R3","first-page":"5360","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1987"},{"key":"2026020211321978400_R4","first-page":"2171","volume-title":"J. Immunol.","year":"1988"},{"key":"2026020211321978400_R5","first-page":"2383","volume-title":"Eur. J. Immunol.","year":"1997"},{"key":"2026020211321978400_R6","first-page":"1803","volume-title":"J. Exp. Med.","year":"1990"},{"key":"2026020211321978400_R7","first-page":"1095","volume-title":"Eur. J. Immunol.","year":"1992"},{"key":"2026020211321978400_R8","first-page":"2101","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020211321978400_R9","first-page":"22","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026020211321978400_R10","first-page":"24341","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020211321978400_R11","first-page":"980","volume-title":"Immunogenetics","year":"2002"},{"key":"2026020211321978400_R12","first-page":"495","volume-title":"Nat. Gen.","year":"2000"},{"key":"2026020211321978400_R13","first-page":"325","volume-title":"Neurosci. Lett.","year":"2002"},{"key":"2026020211321978400_R14","first-page":"614","volume-title":"Mult. Scler.","year":"2004"},{"key":"2026020211321978400_R15","first-page":"22","volume-title":"Nat. Genet.","year":"2001"},{"key":"2026020211321978400_R16","first-page":"23","volume-title":"Nat. Genet.","year":"2001"},{"key":"2026020211321978400_R17","first-page":"168","volume-title":"Genes Immun.","year":"2003"},{"key":"2026020211321978400_R18","first-page":"79","volume-title":"Genes Immun.","year":"2003"},{"key":"2026020211321978400_R19","first-page":"1892","volume-title":"AIDS","year":"2001"},{"key":"2026020211321978400_R20","first-page":"4395","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1982"},{"key":"2026020211321978400_R21","first-page":"135","volume-title":"Cytometry","year":"1994"},{"key":"2026020211321978400_R22","first-page":"51","volume-title":"Transplant. Proc.","year":"2005"},{"key":"2026020211321978400_R23","first-page":"777","volume-title":"Curr. Opin. Struct. Biol.","year":"1997"},{"key":"2026020211321978400_R24","first-page":"351","volume-title":"Immunity","year":"1994"},{"key":"2026020211321978400_R25","first-page":"88","volume-title":"Science","year":"1998"},{"key":"2026020211321978400_R26","first-page":"764","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026020211321978400_R27","first-page":"441","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026020211321978400_R28","first-page":"1479","volume-title":"J. Immunol.","year":"2005"},{"key":"2026020211321978400_R29","first-page":"189","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026020211321978400_R30","first-page":"183","volume-title":"Nature","year":"1990"},{"key":"2026020211321978400_R31","first-page":"423","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020211321978400_R32","first-page":"899","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020211321978400_R33","first-page":"5997","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2003"},{"key":"2026020211321978400_R34","first-page":"2377","volume-title":"Hum. Mol. Genet.","year":"2004"},{"key":"2026020211321978400_R35","first-page":"165","volume-title":"Nat. Rev. Genet.","year":"2001"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/176\/2\/931\/62634134\/931.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/176\/2\/931\/62634134\/931.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:32:34Z","timestamp":1770049954000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/176\/2\/931\/8034197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2006,1,15]]},"published-print":{"date-parts":[[2006,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.176.2.931","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,1]]},"published":{"date-parts":[[2006,1]]}}}