HLA-restricted cytotoxicity against male-specific (H-Y) antigen after acute rejection of an HLA-identical sibling kidney: clonal distribution of the cytotoxic cells.

A 22-year-old previously nonsensitized female patient (HLA-A2,28; B7,14; DR1,2) received a kidney from her HLA-identical brother. She irreversibly rejected the graft 2 1/2 weeks later. In vitro tests performed 6 weeks after the graft loss, using recipient responding and donor-stimulating and target cells, revealed a weak mixed lymphocyte culture (MLC) response and negative direct cell-mediated lympholysis (CML), but strong cytotoxicity against donor target cells after priming in MLC. Both MLC and CML tests using donor-responding cells and recipient-stimulating and target cells were negative. When the patient's cytotoxic cells were tested on a panel of target cells from nonrelated donors, a significant CML was only found against target cells from male donors sharing HLA-A2 and/or B7 with the patient, not with male target cells sharing A28 or B14. By using cold target inhibition tests, two separate populations of male-specific cytotoxic cells could be demonstrated. The one was restricted by HLA-A2, the other by B7. These findings indicate that a self-HLA-restricted cytotoxicity against a male-specific minor histocompatibility antigen was a major cause of the rejection in this case.