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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 15, 2008 Accepted October 18, 2008 High avidity myeloid leukemia-associated antigen-specific CD8+ T cells preferentially reside in the bone marrow J. Joseph Melenhorst, Phillip Scheinberg, Pratip K. Chattopadhyay, Emma Gostick, Kristin Ladell, Mario Roederer, Nancy F. Hensel, Daniel C. Douek, A. John Barrett, and David A. Price* Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom * Corresponding author; email: priced6{at}cardiff.ac.uk. 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 post-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 immunological prognosticators of clinical outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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