Cytotoxic T cells recognizing minor transplantation antigens, and possibly a variant of the HLA-B8 molecule. Cause of rejection of an HLA-identical sibling kidney transplant?

A male uremic patient was first transplanted with a kidney from a female cadaveric donor. The kidney was rejected after two weeks. He was retransplanted approximately one year later with a kidney from his HLA-identical sister. This graft was also irreversibly rejected after one week. No serum antibodies could be detected against the sibling donor before or after transplantation, but the recipient had formed donor-specific cytotoxic T lymphocytes (CTLs). The CTLs were cloned, and clones with two different specificities were obtained. One clone lysed target cells from the donor, from some other family members, and from 50% of a panel sharing HLA-B15 with the recipient. It may recognize a minor transplantation antigen, that is restricted by HLA-B15. The other clone lysed target cells from the donor, from all HLA-B8-positive family members (except the recipient), and from third-party cell donors sharing HLA-B8 with the recipient. When CTLs from third-party individuals were induced toward HLA-B8, target cells from all HLA-B8-positive family members were lysed, except those from the recipient. This indicates that the recipient may have inherited a variant of HLA-B8 that is not detectable by antibodies but by CTLs. These donor-specific CTLs may have contributed to the rejection of the HLA-identical sibling transplant.