{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:40:32Z","timestamp":1790304032032,"version":"4.1.0"},"reference-count":38,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The interaction of von Willebrand factor (vWF) with the platelet receptor glycoprotein Ib\u03b1 (GPIb\u03b1) is important for platelet adhesion at high shear stress. Two functionally important antigenic areas within GPIb\u03b1 were identified through the characterization of 5 new inhibitory anti-GPIb monoclonal antibodies (mAbs). The binding sites of 3 of these anti-GPIb mAbs, which were intercompeting and potently inhibiting shear stress\u2013induced binding of vWF, were mapped within the N-terminal amino acid (aa) 1-59 area by the use of canine-human chimeras. These antibodies, however, had little or no effect (approximately 40% inhibition) on the binding of vWF induced by either botrocetin or ristocetin. On the other hand, the anti-GPIb mAbs 24G10 and 6B4, which blocked GPIb-vWF binding under all conditions examined, bound to 2 different regions of GPIb\u03b1, aa 1-81 and aa 201-268, respectively. The epitope for 6B4 was further narrowed by phage display revealing 2 sets of peptide sequences aligning within aa 259-262 and aa 230-242. In the latter region of GPIb\u03b1, the gain-of-function platelet-type von Willebrand disease (PT-vWD) mutations have been identified. Alignment was partially confirmed because the binding of 6B4 to recombinant GPIb\u03b1 fragments carrying either one of the PT-vWD mutations was considerably impaired but not completely abolished. In contrast, mAb 24G10 bound more strongly to mutant PT-vWD GPIb\u03b1. However, although 24G10 competed with 6B4 for binding to platelets, it bound to an epitope within aa 1-81 of GPIb\u03b1. In conclusion, 2 functionally important areas within GPIb\u03b1 were identified: one localized within the leucine-rich repeat N-terminal aa 1-59 area and one composed of residues aa 1-81 in close contact with aa 201-268. Moreover, further support is provided for the existence of an intramolecular interaction between the N-terminal flanking (aa 1-81) and C-terminal flanking (aa 201-268) regions.<\/jats:p>","DOI":"10.1182\/blood.v98.3.652","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"652-660","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":59,"title":["Epitope mapping of inhibitory antibodies against platelet glycoprotein Ib\u03b1 reveals interaction between the leucine-rich repeat N-terminal and C-terminal flanking domains of glycoprotein Ib\u03b1"],"prefix":"10.1182","volume":"98","author":[{"given":"Nancy","family":"Cauwenberghs","sequence":"first","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vanhoorelbeke","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Vauterin","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douwe F.","family":"Westra","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Romo","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Huizinga","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 A.","family":"Lopez","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Berndt","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jola\u0300n","family":"Harsfalvi","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Deckmyn","sequence":"additional","affiliation":[{"name":"From the Laboratory for Thrombosis Research, IRC, K U Leuven Campus Kortrijk, Belgium; the Department of Haematology, University Hospital Utrecht, The Netherlands; the Thrombosis Research Section, Baylor College of Medicine, Houston, TX; the Baker Medical Research Institute, Melbourne, Australia; and the Department of Clinical Biochemistry and Molecular Pathology, University Medical School, University of Debrecen, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021300081440300_B1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1182\/blood.V77.1.5.5","article-title":"Developing relationships: arterial platelet adhesion, glycoprotein Ib, and leucine-rich 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