Human liver allograft acceptance and the "tolerance assay". II. Donor HLA-A, -B but not DR antigens are able to trigger regulation of DTH.

In our initial study of liver transplant recipients using the trans vivo delayed-type hypersensitivity (DTH) assay, we found that in donor derived B-LCL or sonicates of donor leukocytes triggered linked suppression of the response to recall antigens tetanus toxoid (TT) or Epstein-Barr virus (EBV). Since both donor antigen sources contain HLA class I and class II proteins, we wished to determine which donor HLA proteins were responsible for the linked suppression effect. PBMC from four liver transplant recipients with donor-specific DTH regulation were studied. Surprisingly, we found that single donor HLA-A or B antigens (4/4 patients) but not single HLA-DR (0/4) donor antigens triggered linked suppression of DTH. A dose response study of two patients revealed that donor-type HLA-DR antigens (0.5-500ng) were not capable of triggering any linked suppression; however, as little as 500pg of donor-type HLA-class I protein triggered linked suppression of DTH response to a recall antigen. These findings may have implications for the differential impacts of class I vs class II mismatching in organ transplantation. On a practical level, they indicate that soluble HLA-A and B antigens are the proper choice for detection of DTH regulation as part of a "tolerance assay" in human liver transplant recipients.