Blood, 15 April 2002, Vol. 99, No. 8, pp. 3027-3032
TRANSPLANTATION
The DBY gene codes for an HLA-DQ5-restricted human
male-specific minor histocompatibility antigen involved in
graft-versus-host disease
Mario H. J. Vogt,
Joost W. van den Muijsenberg,
Els Goulmy,
Eric Spierings,
Petra Kluck,
Michel G. Kester,
Ronald A. van
Soest,
Jan W. Drijfhout,
Roel Willemze, and
J. H. Frederik Falkenburg
From the Departments of Hematology, and
Immunohematology and Blood Transfusion, Leiden University
Medical Center, The Netherlands.
Graft rejection or graft-versus-host (GVH) disease after
HLA-identical stem cell transplantation is the result of recognition of
minor histocompatibility antigens (mHags) by immunocompetent T
lymphocytes from recipient or donor origin, respectively. Cytolytic T
lymphocyte (CTL) clones can be isolated during graft rejection and GVH
disease to identify mHags and their corresponding genes. Thus far, all
human mHags identified appeared to be HLA class I-restricted. Here, we
report the characterization of the first human HLA class II-restricted
sex-linked mHag involved in GVH disease. Previously, we isolated an
HLA-DQ5-restricted CD4+ CTL clone from a male patient with
chronic myeloid leukemia who developed acute GVH disease grade III-IV
after transplantation of HLA genotypically identical female stem cells.
Using a panel of female HLA-DQ5+ EBV cells that we stably
transfected with Y chromosome-specific genes, we determined that the
HLA class II male-specific mHag (H-Y) was encoded by the Y
chromosome-specific gene DBY. The H-Y epitope was
localized in the DBY protein using female HLA-DQ5+
peripheral blood mononuclear cells loaded with DBY protein fragments. The minimal peptide sequence leading to maximal recognition by the
specific HLA-DQ5-restricted CTL clone was characterized as the
12-amino acid sequence HIENFSDIDMGE. Although the epitope differed by
3 amino acids from its X-homolog DBX, only 2 polymorphisms were shown
to be essential for recognition by the CTL clone.
