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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 Freese, A. Articles by Zavazava, N. Search for Related Content PubMed PubMed Citation Articles by Freese, A. Articles by Zavazava, N. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2002, Vol. 99, No. 9, pp. 3286-3292 IMMUNOBIOLOGY HLA-B7 -pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses Anja Freese and Nicholas Zavazava From the Department of Internal Medicine, University of Iowa Hospitals and Clinics and VA Medical Center, Iowa City, and DAKO GmbH, Hamburg, Germany. Chronic rejection of transplanted allografts is the major cause of graft loss after clinical solid organ transplantation. Recent data link the indirect presentation of allopeptides to chronic graft loss; thus, identification of immunodominant epitopes on major histocompatibility complex (MHC) antigens could significantly contribute to establishing novel ways for monitoring and managing chronic rejection. Here, we show that synthetic allo-MHC-derived peptides covering the polymorphic region 56 to120 of HLA-B7 modulate alloresponses. In particular, the 2 -pleated sheet-derived peptides covering residues 91 to 105 and 96 to 120, respectively, but not sequences from the 1 helix, were presented by autologous peripheral blood lymphocytes to induce T-cell proliferation. In addition, the 2 -pleated sheet-derived peptides and the 1-derived peptide residues 60 to 75 abrogated lysis of HLA-B7 target cells by anti-HLA-B7 cytotoxic T lymphocytes (CTLs). Although most residues between 91 and 120 are normally not directly accessible to T cells, our results indicate that peptides derived from the lower surface of the peptide-binding groove of HLA-B7 are immunodominant in HLA-B7 alloresponses. To characterize the binding and stability of allopeptides to T cells, the 62-70 peptidederived from the 60-75 allopeptide that blocked cytotoxicity of anti-HLA-B7 CTLwas synthesized and coupled with fluorescein isothiocyanate. The peptide specifically labeled anti-B7 CTL, but not anti-HLA-A2 CTL as measured by flow cytometry. Peptide binding to CTL was specific at 4°C and remained stable for 12 hours, whereas it remained stable for less than 2 hours at 37°C. These studies allow the identification of HLA-B7 T-cell epitopes and reveal for the first time a novel, previously unrecognized application of synthetic HLA-derived allopeptides to visualize alloreactive T cells. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Fried, M. Berg, B. Sharma, S. Bonde, and N. Zavazava Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells J. Leukoc. Biol., September 1, 2005; 78(3): 595 - 604. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020