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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Barron-Casella, E. A. Articles by Casella, J. F. Search for Related Content PubMed PubMed Citation Articles by Barron-Casella, E. A. Articles by Casella, J. F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 9 (May 1), 1999: pp. 2959-2967 Construction of a Human Platelet Alloantigen-1a Epitope(s) Within Murine Glycoprotein IIIa: Identification of Residues Critical to the Conformation of the Antibody Binding Site(s) Emily A. Barron-Casella, Gaia Nebbia, Ophelia C. Rogers, Karen E. King, Thomas S. Kickler, and James F. Casella From the Departments of Pediatrics and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. The human platelet alloantigen 1 system (HPA-1) is determined by a polymorphism at position 33 in the N-terminus of human glycoprotein IIIa (GPIIIa). This naturally occurring substitution creates a conformation in the HPA-1a allelic form that can be antigenic when presented to an individual expressing the HPA-1b form. Anti-HPA-1a antibodies generated by this immune response can lead to the destruction of platelets, as seen in the clinical disorders, neonatal alloimmune thrombocytopenia (NAIT) and posttransfusion purpura (PTP). To understand better the structural requirements for recognition by these pathogenic antibodies, we investigated the N-terminal 66 amino acids from the HPA-1a form of human GPIIIa and the analogous amino acids from the nonimmunogenic murine homolog. Our objectives were to define further the boundaries of the HPA-1a epitope(s) in the N-terminus of human GPIIIa, to isolate the murine 5' nucleotide sequence and compare the deduced murine N-terminal sequence to that of human, and to mutate the murine sequence systematically to include an HPA-1a epitope(s). Murine amino acids that differed from human were changed by site-directed mutagenesis to the analogous residues in the HPA-1a form of human GPIIIa, starting and radiating from murine position 33 (site of human polymorphism). This systematic approach allowed us to pinpoint amino acids critical to a conformation recognized by anti-HPA-1a antibodies. Our results show that an HPA-1a epitope can be created within the N-terminus of murine GPIIIa and raise the possibility that murine models of HPA-1a sensitization can be developed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. A. Watkins, E. Schaffner-Reckinger, D. L. Allen, G. J. Howkins, N. H. C. Brons, G. A. Smith, P. Metcalfe, M. F. Murphy, N. Kieffer, and W. H. Ouwehand HPA-1a phenotype-genotype discrepancy reveals a naturally occurring Arg93Gln substitution in the platelet beta 3 integrin that disrupts the HPA-1a epitope Blood, March 1, 2002; 99(5): 1833 - 1839. [Abstract] [Full Text] [PDF]

	Copyright © 1999 by American Society of Hematology         Online ISSN: 1528-0020