Chapter Category: MHC

From the book Minor Histocompatibility Antigens: From the Laboratory to the Clinic

Identification of Human Minor Histocompatability Antigens: Towards

Els Goulmy

Minor histocompatibility (H) antigens are readily studied in the HLA identical Bone Marrow Transplantation (BMT) setting. BMT in combination with chemoradiotherapy is used as a treatment for severe aplastic anemia, leukemia, and other hematologic malignancies. The ideal transplant situation is when BM donor and recipient have identical MHC antigens. The results of clinical BMT reveal that the selection of such MHC identical donors does not guarantee avoidance of two of the major drawbacks of allogeneic BMT, GVHD and leukemic relapse. GVHD occurs, depending on the age of the recipient and the amount of T-cell depletion of the graft, in 15-35% of HLA genotypically identical donor/recipient pairs. T cell depletion of the donor marrow inoculum shows a reduction in the incidence and severity of GVHD but coincides with an increase of leukemia relapse. So the presence of some mature T cells in the donor bone marrow inoculum is essential for graft acceptance. T cells are also responsible for GVHD and most probably the beneficial Graft-versus-Leukemia (GVL) effect. Several clinical studies indicate a direct relationship between the GVL effect and acute and chronic GVHD. In syngeneic BMT between identical twins and in recipients of autologous BMT, relapse rates are high. No MHC or minor H antigen disparities exist and thus no alloreactivity can be induced. In contrast, in allogeneic BMT the relapse rates are significantly lower and a relationship is seen between the GVL effect and acute and chronic GVH. Since the GVH and GVL activities occur in allogeneic, HLA identical BMT, alloreactive donor T cells are likely to play an important role in these activities. In the HLA identical situation, these alloreactive donor T cells appear to be directed at the patient’s disparate minor H antigens.

Taken from the book

Minor Histocompatibility Antigens: From the Laboratory to the Clinic

Edited by: Els Goulmy

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