Exogenous Addition of Minor H Antigen HA-1+ Dendritic Cells to Skin Tissues Ex Vivo Causes Infiltration and Activation of HA-1-Specific Cytotoxic T Cells

T cells specific for hematopoietic system restricted minor Histocompatibility (H) antigens target normal and malignant hematopoietic cells. Thus, cellular immune responses against the latter miHAS eradicate the recipient’s hematopoiesis including residual leukemic cells after HLA-matched minor H antigen-mismatched stem-cell transplantation (SCT). However, there are controversial reports on the role of HA-1 in the development of graft-versus-host-disease (GVHD) as well. Here, we address the behavior of HA-1-specific cytotoxic T cells (CTLs) in an ex vivo in situ skin explant model wherein HA-1-expressing dendritic cells (DCs) were added as antigen-presenting cells (APCs). Infiltration and activation of HA-1 CTLs occurred only in those cases where both HLA-A2 and HA-1 were expressed, either by the skin or by the DCs, or by the combination of HLA-A2⁺ skin and HA-1⁺ DCs. These results point toward the role of recipient’s HA-1⁺ DCs in the chimeric patient suffering from GVHD after HA-1-mismatched SCT. Although in our model the infiltrated and activated CTLs did not cause skin tissue destruction, our results provide a first step in understanding the reported association of HA-1 mismatching with clinical GVHD.

Key Words: Minor histocompatibility antigen, Graft-versus-host disease, Human skin, Antigen/peptide/epitopes, Dendritic cells