HA-1 AND THE SMCY-DERIVED PEPTIDE FIDSYICQV (H-Y) ARE IMMUNODOMINANT MINOR HISTOCOMPATIBILITY ANTIGENS AFTER BONE-MARROW TRANSPLANTATION

Background. Allogeneic bone marrow donors can be incompatible at diffe rent levels, Even HLA-identical pairs will be still incompatible for n umerous minor histocompatibility antigens (mHag). Nevertheless, some i ncompatibilities are found to be associated with an increased risk of graft-versus-host disease (GVHD), which could be related to the way th e immune system recognizes these antigens. Methods. We determined the specificity of cytotoxic T-cell clones isolated during acute GVHD or d uring bone marrow graft rejection in patients (n=14) transplanted with marrow from donors who were histoincompatible for different minor and /or major histocompatibility antigens, Results. We found a clear hiera rchy among the different types of histoincompatibilities. In three com binations mismatched for a class I allele, all 27 clones isolated duri ng GVHD were specific for the incompatible HLA molecule. In the 11 cla ss I-identical combinations, 14 different mHags were recognized. The m Hag HA-1, known to have a significant impact on the development of GVH D, was recognized in the two HA-1-incompatible combinations. In one of these combinations, which was sex mismatched, all 56 clones analyzed were directed against HA-1, demonstrating the dominance of this mHag. In the four HA-1-compatible, sex-mismatched combinations, the anti-H-Y response was directed against one immunodominant epitope rather than against multiple Y-chromosome-encoded epitopes. All male specific cyto toxic T lymphocytes (n=15) recognized the same high-performance liquid chromatography-purified peptide fraction presented by T2 cells. Moreo ver, all cytotoxic T lymphocytes tested (n=6) were specific for the SM CY-derived peptide FPDSYICQV, originally described as being the H-Y ep itope recognized in the context of HLA-A0201. Conclusions, Some histo compatibility antigens are recognized in an immunodominant fashion and will therefore be recognized in the majority of mismatched combinatio ns. Only for such antigens, correlations between mismatches and the oc currence of GVHD or graft rejections will be found.