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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2238-2244. Prepublished online as a Blood First Edition Paper on November 7, 2008; DOI 10.1182/blood-2008-04-151969. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-151969v1 113/10/2238    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 Citing Articles via Google Scholar Google Scholar Articles by Melenhorst, J. J. Articles by Price, D. A. Search for Related Content PubMed PubMed Citation Articles by Melenhorst, J. J. Articles by Price, D. A. Related Collections Immunobiology Transplantation Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY High avidity myeloid leukemia-associated antigen-specific CD8+ T cells preferentially reside in the bone marrow J. Joseph Melenhorst1, Phillip Scheinberg1,2, Pratip K. Chattopadhyay3, Emma Gostick4, Kristin Ladell4, Mario Roederer3, Nancy F. Hensel1, Daniel C. Douek2, A. John Barrett1, and David A. Price2,4 1 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; 2 Human Immunology Section and 3 Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD; and 4 Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom The activity of allogeneic CD8+ T cells specific for leukemia-associated antigens (LAAs) is thought to mediate, at least in part, the curative effects of hematopoietic stem cell transplantation (HSCT) in myeloid malignancies. However, the identity and nature of clinically relevant LAA-specific CD8+ T-cell populations have proven difficult to define. Here, we used a combination of coreceptor-mutated peptide-major histocompatibility complex class I (pMHCI) tetramers and polychromatic flow cytometry to examine the avidity profiles, phenotypic characteristics, and anatomical distribution of HLA A*0201-restricted CD8+ T-cell populations specific for LAAs that are over-expressed in myeloid leukemias. Remarkably, LAA-specific CD8+ T-cell populations, regardless of fine specificity, were confined almost exclusively to the bone marrow; in contrast, CD8+ T-cell populations specific for the HLA A*0201-restricted cytomegalovirus (CMV) pp65495-503 epitope were phenotypically distinct and evenly distributed between bone marrow and peripheral blood. Furthermore, bone marrow-resident LAA-specific CD8+ T cells frequently engaged cognate antigen with high avidity; notably, this was the case in all tested bone marrow samples derived from patients who achieved clinical remission after HSCT. These data suggest that concomitant examination of bone marrow specimens in patients with myeloid leukemias might yield more definitive information in the search for immunologic prognosticators of clinical outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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