Bone Marrow–Allograft Rejection by T Lymphocytes Recognizing a Single Amino Acid Difference in HLA-B44

Abstract

BONE marrow from unrelated donors is increasingly being transplanted for the treatment of patients with leukemia, aplastic anemia, and lethal congenital disorders of hematopoiesis and immunologic function. National and international registries of HLA-typed volunteer donors have been developed to optimize HLA matching between unrelated donors and recipients.^{1 , 2} The fate of marrow grafts depends on many factors, including conditioning regimens, the composition of the cells in the graft, immunosuppression after transplantation, and the degree of histocompatibility between donor and recipient. Clinically serious graft-versus-host disease occurs in 20 to 50 percent of patients receiving marrow grafts from HLA-identical siblings, and some measure of the disease occurs in 60 to 80 percent.³ Depletion of T lymphocytes from the marrow graft before transplantation has decreased the frequency of graft-versus-host disease and in some studies has eliminated severe disease.⁴ This practice has, however, been associated with a substantial increase in the occurrence of graft failure or rejection.^{4 5 6} Graft rejection is also more likely when the donor and recipient have different HLA antigens,^{4 , 7} irrespective of the type of graft (i.e., unmodified or T-cell depleted). Rejection of a marrow allograft is in most instances an immunologic process mediated by T lymphocytes.^{8 9 10 11 12 13} Allogeneic HLA Class I antigens are recognized by CD8+ T lymphocytes, whereas Class II antigens are recognized by CD4+ T lymphocytes.^{14 15 16 17}