Graft-versus-host disease associated T helper cell responses specific for minor histocompatibility antigens are mainly restricted by HLA-DR molecules.

Graft-versus-host reactions are mediated by subpopulations of donor T cells and can be attributed to host specific minor histocompatibility (mH) antigens. We isolated strong anti-host mH antigen proliferative T cell lines, LG2, PN2, and LH3, from three patients suffering from acute graft-versus-host disease (GVHD). To study the role of the different major histocompatibility complex (MHC) molecules in the anti-host mH antigen specific proliferative response, the reactivities of the three T cell lines were analysed in primed lymphocyte test (PLT) assays against panels of stimulator cells obtained from unrelated blood donors. LG2 and LH3 stimulating determinants were commonly detected in the unrelated panel, whereas the PN2 T cell line recognized a rare specificity. The responses were associated with the presence of self HLA-DR molecules on the stimulator cells, although not all DR sharing stimulator cells were recognized. The proliferative responses of LG2, LH3 and PN2 cells could be blocked by monoclonal antibodies (MoAbs) against HLA-DR, but not by MoAbs against HLA-A/B/Cw, HLA-DQ or -DP. At the responder cell level, depletion of CD4 cells as well as blocking with CD4 specific MoAbs abrogated the specific responses of the three T cell lines. Our findings suggest that anti-host Th cell responses activated in the acute phase of GVHD are directed against both frequent and rare mH antigens, are mediated by CD4 + ve class II restricted Th cells, and use the HLA-DR molecule as a common restriction element for mH antigen presentation.