A limited number of HLA epitopes are recognized from HLA class I-specific antibodies detected in the serum of sensitized patients

The goal of this study was to evaluate the epitope specificity of HLA class I-specific antibodies detected in the serum of sensitized patients awaitin g retransplantation. The study group consisted of 22 sensitized from previo us graft patients, who produced stable IgG HLA class I-specific antibodies. A total of 60 serum samples were screened and analyzed by two techniques i n parallel: the antihuman globulin augmented CDC (AHG-CDC) technique and an ELISA technique. All recipients and donors were typed for class I HLA anti gens by a standard lymphocytotoxicity technique. The epitope identification was based on class I HLA antigens sequencing, where the multiple immunogen ic epitopes are differentially shared among various HLA antigens. The uniqu e epitope configuration on one HLA antigen represents the private epitope o f the specific HLA antigen while epitopes shared by more than one HLA antig en represent public determinants. In some HLA antigens (HLA-A1), more than one private epitope has been defined, while in others (HLA-B35, -B51), the private epitopes are not yet known. In a total of 36 antibody reactivity pa tterns, the majority of the definable IgG HLA class I-specific antibodies c orresponded to the A-locus (75%), and only 25% had specificities against th e B-locus antigens, although the number of incompatibilities concerning bot h loci were almost identical (29 for the HLA antigens of the A-locus and 26 for those of B-locus). All patients produced HLA class I-specific antibodi es with specificities against: the private epitopes of the immunogenic mism atched HLA antigen(s). In 6/21 cases (28.6%), HLA class I alloreactivity sp reading to nongraft HLA antigens was detected and 9 public (shared) immunog enic alloepitopes were recognized. In conclusion, appling the epitope analy sis of HLA class I-specific antibodies produced by sensitized from previous graft patients, we were able to define the immunogenic alloepitopes. We co nsider that the immunogenic alloepitopes, during transplantation course, ar e mainly private epitopes of mismatched HLA antigens and, in certain cases, shared epitopes between the donor alloantigens and other HLA antigens. Thi s knowledge may offer the potential of transplanting sensitized patients th rough improved donor selection. Human Immunology! 61, 705-710 (2000). (C) A merican Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.