The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease.

Blood
Mario H VogtJ H Frederik Falkenburg

Abstract

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 sp...Continue Reading

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