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Blood, 22 October 2009, Vol. 114, No. 17, pp. 3684-3692. Prepublished online as a Blood First Edition Paper on August 25, 2009; DOI 10.1182/blood-2009-03-208017. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-03-208017v1 114/17/3684    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 CrossRef Google Scholar Articles by Stumpf, A. N. Articles by Griffioen, M. PubMed PubMed Citation Articles by Stumpf, A. N. Articles by Griffioen, M. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Identification of 4 new HLA-DR–restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity Anita N. Stumpf1, Edith D. van der Meijden1, Cornelis A. M. van Bergen1, Roel Willemze1, J. H. Frederik Falkenburg1, and Marieke Griffioen1 1 Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands Potent graft-versus-leukemia (GVL) effects can be mediated by donor-derived T cells recognizing minor histocompatibility antigens (mHags) in patients treated with donor lymphocyte infusion (DLI) for relapsed hematologic malignancies after HLA-matched allogeneic stem cell transplantation (alloSCT). Donor-derived T cells, however, may not only induce GVL, but also mediate detrimental graft-versus-host disease (GVHD). Because HLA-class II is under noninflammatory conditions predominantly expressed on hematopoietic cells, CD4+ T cells administered late after alloSCT may selectively confer GVL without GVHD. Although a broad range of different HLA-class I–restricted mHags have been identified, the first 2 autosomal HLA-class II–restricted mHags have only recently been characterized. By screening a recombinant bacteria cDNA expression library, we identified 4 new HLA-class II–restricted mHags recognized by CD4+ T cells induced in a patient with relapsed chronic myeloid leukemia who achieved long-term complete remission and experienced only mild GVHD of the skin after DLI. All CD4+ T cells were capable of recognizing the mHags presented by HLA-DR surface molecules on primary hematopoietic cells, but not on skin-derived (cytokine-treated) fibroblasts. The selective recognition of hematopoietic cells as well as the balanced population frequencies and common HLA-DR restriction elements make the novel mHags possible targets for development of immunotherapeutic strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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