Ed or Histocompatibility Antigens Are Differentially Expressed on Human Hematopoietic Progenitor Cells by Paul J . Voogt, Els Goulmy,

Allogeneic bone marrow transplantation (BMT)' has become a major therapeutic modality in the treatment of various malignant and nonmalignant hematologic disorders (1-6) . However, graft-vs.-host disease (GuHD) causes much morbidity and mortality after transplantation (7, 8) . Since GvHD is mediated by immunocompetent T cells in the graft (9, 10), depletion of T cells from the bone marrow graft has been successfully applied to reduce the incidence of this complication (11, 12) . On the other hand, T cell depletion from the graft has led to an increased incidence of graft failure (13-16), which could in part be prevented by increasing the intensity of the pretransplant conditioning regimen (16-20) . As a result of the genetic disparity between donor and recipient, graft failure may be due to an immune-mediated rejection by immunocompetent cells in the recipvided that these cells are not eliminated by the pretransplant conditioning and/or by the donor T cells present in the graft . In HLA-nonidentical transplants, the high incidence of graft rejection (21, 22) can be explained by the general tissue distribution of these histocompatibiiity antigens, and, in particular, by the expression of HLA class I and class II antigens on hematopoietic progenitor cells (HPC) (23-26) . However, after the introduction of T cell depletion of the graft to prevent GuHD, -157o graft rejections have also been observed in HLA-identical transplants (13-16) . In these cases, antigenic determinants outside the HLA system, called minor histocompatibility (mH) antigens (27), are likely to be involved in the pathogenesis of graft rejection. If mH antigens are expressed on HPC, an immune response in the recipient, directed against these target structures on donor cells, may lead to elimination of the hematopoietic stem cells from the graft . Therefore, mapping of mH antigens on HPC is of major importance for understanding the mechanism of rejection of the hematopoietic graft in bone marrow transplantation .