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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4817-4826.
Prepublished online as a Blood First Edition Paper on February 25, 2008; DOI 10.1182/blood-2007-06-096313.


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Submitted June 18, 2007
Accepted February 16, 2008

DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells

Kellie V. Rosinski, Nobuharu Fujii, Jeffrey K. Mito, Kevin K.W. Koo, Suzanne M. Xuereb, Olga Sala-Torra, James S. Gibbs, Jerald P. Radich, Yoshiki Akatsuka, Benoit J. Van den Eynde, Stanley R. Riddell, and Edus H. Warren*

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Laboratory of Viral Diseases, NIAID, Bethesda, MD, United States
Department of Medicine, University of Washington, Seattle, WA, United States
Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan
Ludwig Institute for Cancer Research, Brussels, Belgium

* Corresponding author; email: ehwarren{at}u.washington.edu.

The Y chromosome encodes male-specific minor histocompatibility (H-Y) antigens that stimulate T- and B-lymphocyte responses after sex-mismatched allogeneic hematopoietic cell transplantation (HCT). A CD8+ cytotoxic T lymphocyte (CTL) clone that recognizes a novel HLA-B*2705-restricted H-Y antigen encoded by the DDX3Y gene was isolated from a male who had received a hematopoietic cell graft from his human leukocyte antigen (HLA)-identical sister. The antigenic peptide is a decamer that differs from the homologous DDX3X-encoded peptide at four positions. Expression of DDX3Y and of the H-Y epitope that it encodes was examined by quantitative PCR and by CTL recognition assays. Expression of DDX3Y is detected in all myeloid and lymphoid leukemic cells that carry an intact Y chromosome. Moreover, the DDX3Y-encoded H-Y epitope is presented on the surface of both myeloid and lymphoid leukemic cells from male HLA-B*2705+ patients. DDX3Y-specific CTL prevent engraftment of human acute leukemia in non-obese diabetic/severe combined immune deficient mice, demonstrating that the DDX3Y-encoded H-Y antigen is also expressed in leukemic stem cells. These results demonstrate that CD8+ T cell responses against DDX3Y have the potential to contribute to graft-versus-leukemia (GVL) activity after female into male allogeneic HCT. This study is registered at http://clinicaltrails.gov as NCT00107354.


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