Discovery of minor histocompatibility antigens as targets for immunotherapy

<table align="center" border="0" cellpadding="0" cellspacing="0" style="width:100.0%;" width="100%">\n\t<tbody>\n\t\t<tr>\n\t\t\t<td>\n\t\t\t\t<p>\n\t\t\t\t\tAllogeneic stem cell transplantation (alloSCT) can be a curative treatment for hematological malignancies. However, the desired anti-tumor or Graft-versus-Leukemia (GvL) effect is often accompanied by undesired side effects, a complication known as Graft-versus-Host Disease (GvHD). GvL and GvHD are both caused by donor-derived T-cells recognizing alloantigens on patient cells. The main challenge for treatment of hematological malignancies with alloSCT is to evoke effective GvL reactivity, while limiting the risk of severe GvHD. In HLA-matched alloSCT, alloantigens recognized by donor T-cells are polymorphic peptides presented by HLA surface molecules on patient cells, the so-called minor histocompatibility antigens (MiHA). MiHA with hematopoiesis-restricted expression are relevant targets for immunotherapy, since donor T-cells for these MiHA will attack the malignant cells of the patient, while sparing healthy hematopoietic cells of donor origin. This thesis focused on efficient characterization of MiHA with potential therapeutic relevance, including MiHA that are encoded or produced by alternative transcripts, by analysis of in vivo immune responses after alloSCT. This analysis is relevant to provide insight into the immunobiology of GvL and GvHD after alloSCT and to identify MiHA with restricted expression on hematopoietic cells as potential targets for T-cell therapy to stimulate GvL reactivity after alloSCT without GvHD.</p>\n\t\t\t</td>\n\t\t</tr>\n\t</tbody>\n</table>\n<div style="clear:both;">\n\t </div>\n