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

Abstract:

: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 4 positions. Expression of DDX3Y and of the H-Y epitope that it encodes was examined by quantitative polymerase chain reaction (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 CTLs prevent engraftment of human acute leukemia in nonobese 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://clinicaltrials.gov as NCT00107354.

journal_name

Blood

journal_title

Blood

authors

Rosinski KV,Fujii N,Mito JK,Koo KK,Xuereb SM,Sala-Torra O,Gibbs JS,Radich JP,Akatsuka Y,Van den Eynde BJ,Riddell SR,Warren EH

doi

10.1182/blood-2007-06-096313

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

4817-26

issue

9

eissn

0006-4971

issn

1528-0020

pii

blood-2007-06-096313

journal_volume

111

pub_type

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