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Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors.

ABSTRACT: Minor histocompatibility antigens (mHAs) recognized by donor T cells play a central role as immunologic targets of graft-versus-host disease (GVHD) and graft versus leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Men who have undergone sex-mismatched allogeneic HSCT are at high risk for GVHD because of immune responses directed against mHAs encoded by genes on the Y chromosome (termed H-Y antigens). We hypothesized that the immunogenicity of mHAs results in a coordinated response involving B cells as well as T cells. To test this, we measured antibody responses to a well-characterized H-Y antigen, dead box RNA helicase Y (DBY), and its homolog, DBX, in 150 HSCT patients. Using Western blot and enzyme-linked immunosorbent assay (ELISA), we found that 50% of male patients who received stem cell grafts from female donors developed antibody responses to recombinant DBY protein. Antibodies to DBY were also detected in 17% of healthy women, but not in healthy men. Antibody responses were directed primarily against areas of amino acid disparity between DBY and DBX. These studies demonstrate that the immune response to mHA includes the generation of specific antibodies and suggests that the serologic response to these antigens may also be useful in the identification of new mHAs.

SUBMITTER: Miklos DB

PROVIDER: S-EPMC1350983 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature

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Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors.

Miklos David B DB Kim Haesook T HT Zorn Emmanuel E Hochberg Ephraim P EP Guo Luxuan L Mattes-Ritz Alex A Viatte Sebastien S Soiffer Robert J RJ Antin Joseph H JH Ritz Jerome J

Blood 20030925 1

Minor histocompatibility antigens (mHAs) recognized by donor T cells play a central role as immunologic targets of graft-versus-host disease (GVHD) and graft versus leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Men who have undergone sex-mismatched allogeneic HSCT are at high risk for GVHD because of immune responses directed against mHAs encoded by genes on the Y chromosome (termed H-Y antigens). We hypothesized that the immunogenicity of mHAs results in a coordinate ...[more]

PMID: 14512314

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Project description:Minor Histocompatibility (H) antigens are major histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)-bound peptides that differ between allogeneic hematopoietic stem cell transplantation (HCT) recipients and their donors as a result of genetic polymorphisms. Some minor H antigens can be used as therapeutic T cell targets to augment the graft-vs.-leukemia (GVL) effect in order to prevent or manage leukemia relapse after HCT. Graft engineering and post-HCT immunotherapies are being developed to optimize delivery of T cells specific for selected minor H antigens. These strategies have the potential to reduce relapse risk and thereby permit implementation of HCT approaches that are associated with less toxicity and fewer late effects, which is particularly important in the growing and developing pediatric patient. Most minor H antigens are expressed ubiquitously, including on epithelial tissues, and can be recognized by donor T cells following HCT, leading to graft-vs.-host disease (GVHD) as well as GVL. However, those minor H antigens that are expressed predominantly on hematopoietic cells can be targeted for selective GVL. Once full donor hematopoietic chimerism is achieved after HCT, hematopoietic-restricted minor H antigens are present only on residual recipient malignant hematopoietic cells, and these minor H antigens serve as tumor-specific antigens for donor T cells. Minor H antigen-specific T cells that are delivered as part of the donor hematopoietic stem cell graft at the time of HCT contribute to relapse prevention. However, in some cases the minor H antigen-specific T cells delivered with the graft may be quantitatively insufficient or become functionally impaired over time, leading to leukemia relapse. Following HCT, adoptive T cell immunotherapy can be used to treat or prevent relapse by delivering large numbers of donor T cells targeting hematopoietic-restricted minor H antigens. In this review, we discuss minor H antigens as T cell targets for augmenting the GVL effect in engineered HCT grafts and for post-HCT immunotherapy. We will highlight the importance of these developments for pediatric HCT.

Dataset Information

Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors.

Publications

Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors.

Similar Datasets

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