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Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2003-01-0260. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0260v1 102/2/621    most recent 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 Spierings, E. Articles by Engelhard, V. H. Search for Related Content PubMed PubMed Citation Articles by Spierings, E. Articles by Engelhard, V. H. Related Collections Immunobiology Transplantation Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 621-629 IMMUNOBIOLOGY The minor histocompatibility antigen HA-3 arises from differential proteasome–mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein Eric Spierings, Anthony G. Brickner, Jennifer A. Caldwell, Suzanne Zegveld, Nia Tatsis, Els Blokland, Jos Pool, Richard A. Pierce, Sahana Mollah, Jeffrey Shabanowitz, Laurence C. Eisenlohr, Peter Van Veelen, Ferry Ossendorp, Donald F. Hunt, Els Goulmy, and Victor H. Engelhard From the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville; Department of Chemistry, University of Virginia, Charlottesville; Department of Microbiology and Immunology and the Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA; and Department of Pathology, University of Virginia, Charlottesville Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen (HLA)–identical allogeneic stem cell transplantation (SCT). To understand the basis of alloimmune responses against minor H antigens, identification of minor H peptides and their antigenicity-determining mechanisms is essential. Here we report the identification of HA-3 and its encoding gene. The HA-3 peptide, VTEPGTAQY (HA-3T), is encoded by the lymphoid blast crisis (Lbc) oncogene. We thus show for the first time that a leukemia-associated oncogene can give rise to immunogenic T-cell epitopes that may have participated in antihost and antileukemic alloimmune responses. Genotypic analysis of HA-3- individuals revealed the allelic counterpart VMEPGTAQY (HA-3M). Despite the lack of T-cell recognition of HA-3- cells, the ThrMet substitution had only a modest effect on peptide binding to HLA-A1 and a minimal impact on recognition by T cells when added exogenously to target cells. This substitution did not influence transporter associated with antigen processing (TAP) transport, but, in contrast to the HA-3T peptide, HA-3M is destroyed by proteasome-mediated digestion. Thus, the immunogenicity of minor H antigens can result from proteasome-mediated destruction of the negative allelic peptide. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. N. Stumpf, E. D. van der Meijden, C. A. 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