Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44

Article Abstract:

Bone marrow transplantation is becoming a more common procedure. The procedure is used in treating leukemia, and in patients with marrow destroyed by chemotherapy or with marrow that is ineffective due to some congenital disorder. While many of the original attempts at bone marrow transplantation used matched bone marrow from donors within the patient's family, it has become increasingly more common to use unrelated donors. In fact, registries are being developed to improve the matches of bone marrow between patient and donor. Bone marrow transplantation has more potential complications, in contrast with many other sorts of transplantation. Not only might the patient's immune system attack and reject the grafted marrow, but immune cells within the grafted marrow may attack the patient's tissue in graft-versus-host disease. Since graft-versus-host disease seems to directly result from grafted T cells, donor bone marrow is now often depleted of T cells prior to transplantation. Unfortunately, the process of T cell depletion also increases the probability that the grafted bone marrow will be rejected. The authors report a case in which T cell depleted bone marrow was rejected by the recipient. The donor and recipient were compatible for the HLA histocompatibility antigens by serological testing and were also shown to be compatible by the mixed lymphocyte test, in which a cellular reaction can often be detected between incompatible antigens. Upon rejection, it was found that the patient had circulating T cells that seemed to react with a difference in the composition of the histocompatibility antigens of only one single amino acid. Both the donor and recipient were HLA-B44, but one was a variant classed as B44.1, while the other was B44.2. Investigation revealed that the only difference between these antigens was a leucine in the 156th position of B44.1, which was replaced by an aspartic acid in B44.2. While it cannot be concluded with certainty that this difference was responsible for the rejection of the grafted bone marrow, the identification within the patient of T cells that recognized this difference strongly suggests that a single amino acid difference may have caused the rejection. (Consumer Summary produced by Reliance Medical Information, Inc.)

HLA antigens, T cells, Histocompatibility antigens

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Pretransplantation blood transfusion revisited

Article Abstract:

Although blood transfusions to potential organ recipients before transplantation enhance survival of the grafted organ, the mechanisms responsible for this have not been characterized. Evidence from animal experiments suggests that such transfusions are beneficial only if blood donor and recipient share at least one common histocompatibility antigen (cell-surface proteins that mediate graft rejection reactions), called human leukocyte antigens (HLA). When donor and recipient are mismatched for certain HLA antigens, components of the immune system (cytotoxic T cells) can be activated that attack donor blood cells. This was tested in humans by studying 23 patients who underwent their first kidney transplantation. The frequency of cytotoxic T-lymphocyte precursor cells directed against donor cells was evaluated before transfusion and after 1, 4, 8, and 16 weeks. Results showed that the frequency of these cells stayed at pre-transfusion levels, or increased, in 13 cases, while the frequency decreased quickly in 10 patients. Further analysis showed that the T-cell response declined only when donor and recipient shared an HLA-A, HLA-B, and HLA-DR antigen (specific loci of the HLA group); at the least, they had to share an HLA-B and an HLA-DR antigen. Thus, blood donors for transplant patients should be HLA-matched in order to induce T-cell tolerance. This may ultimately enhance graft survival. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prevention, Blood transfusion

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Minor histocompatibility antigens and marrow transplantation

Article Abstract:

The high incidence of graft-versus-host disease (GVHD) in recipients of bone marrow from HLA-identical donors indicates that other antigens besides HLA antigens may have an important role in determining transplant success. GVHD occurs when transplanted immune cells attack the recipient's tissues. During immune recognition, foreign antigens are presented to cytotoxic T lymphocytes by the major histocompatibility antigens, or HLA antigens. Certain of these HLA antigens strongly affect a recipient's tolerance of a graft by determining whether a T cell will see the antigen as foreign and kill the cell presenting the antigen. This determination of compatibility between donor and recipient tissue has revealed a group of minor histocompatibility antigens. Two 1996 reports illustrate the significance of these compatibility factors. One report links GVHD to a donor-recipient mismatch in the HA-1 antigen and the other to a donor-recipient mismatch in the CD31 adhesion molecule.

Editorial, Analysis, Graft versus host reaction, Graft vs. host disease

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