{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:50:00Z","timestamp":1777517400789,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,24]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main autoantigen in WG. The relevant peptides responsible for this in vitro proliferation have not been identified. In order to define immunogenic peptides, PBMC of 13 WG patients in remission and 10 healthy controls were tested for proliferation to linear peptides of PR3 and to whole PR3. Fifty overlapping peptides spanning the whole PR3 sequence were synthesized. Peptides were tested in pools of five peptides and as single peptide. PBMC of two WG patients and one healthy control proliferated to whole PR3 and to peptide pools. In addition, 10 WG patients and eight healthy controls that did not proliferate to whole PR3 did proliferate to pools of PR3 peptides. Although more WG patients tended to react to particular peptide pools, no significant difference was seen between lymphocyte proliferation to PR3 peptides of WG patients and that of healthy controls. The pools of peptides recognized were mainly located at the N- and C-terminus of PR3. No correlation was observed between HLA type and proliferation on particular peptide pools. No proliferation of PBMC was observed to single peptides. In conclusion, T cells of WG patients proliferate in vitro more frequently to PR3 peptides than to the whole PR3 protein. Peptides derived from the signal sequence, the propeptide or peptides located at the C-terminus of PR3 induce highest levels of proliferation. No specific PR3 sequence could be identified that was preferentially recognized by PBMC of WG patients compared with controls.<\/jats:p>","DOI":"10.1046\/j.1365-2249.2000.01415.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:24:10Z","timestamp":1047378250000},"page":"504-513","source":"Crossref","is-referenced-by-count":27,"title":["<i>In vitro<\/i>T lymphocyte responses to proteinase 3 (PR3) and linear peptides of PR3 in patients with Wegener's granulomatosis (WG)"],"prefix":"10.1093","volume":"122","author":[{"given":"Y M","family":"Van Der Geld","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University Hospital Groningen, Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M G","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Groningen, Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C F M","family":"Franssen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Groningen, Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Van Der Zee","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P C","family":"Limburg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Groningen, Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C G M","family":"Kallenberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Groningen, Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"2022011221092401500_b1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.7326\/0003-4819-98-1-76","article-title":"Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years","volume":"98","author":"Fauci","year":"1983","journal-title":"Ann Intern Med"},{"key":"2022011221092401500_b2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0140-6736(85)91147-X","article-title":"Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis","volume":"1","author":"Van Der Woude","year":"1985","journal-title":"Lancet"},{"key":"2022011221092401500_b3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1172\/JCI114335","article-title":"Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils","volume":"84","author":"Goldschmeding","year":"1989","journal-title":"J Clin Invest"},{"key":"2022011221092401500_b4","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1182\/blood.V74.6.1888.1888","article-title":"Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase","volume":"74","author":"Niles","year":"1989","journal-title":"Blood"},{"key":"2022011221092401500_b5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1084\/jem.171.1.357","article-title":"Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme","volume":"171","author":"L\u00fcdemann","year":"1990","journal-title":"J Exp Med"},{"key":"2022011221092401500_b6","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1001\/archinte.1989.00390110055012","article-title":"Association between active Wegener's granulomatosis and anticytoplasmic antibodies","volume":"149","author":"Cohen Tervaert","year":"1989","journal-title":"Arch Intern Med"},{"key":"2022011221092401500_b7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ki.1994.239","article-title":"Anti-neutrophil cytoplasmic antibodies: current diagnostic and pathophysiological potential","volume":"46","author":"Kallenberg","year":"1994","journal-title":"Kidney Int"},{"key":"2022011221092401500_b8","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/0002-9343(83)91030-6","article-title":"Pulmonary vasculitis (Wegener's granulomatosis). 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