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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.
Submitted June 18, 2007
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States * 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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