Allogeneic disparities in immunoglobuline-like transcript 5 (ILT5) induce potent antibody responses in hematopoietic stem cell transplant recipients Short title: ILT5 specific antibodies in HSCT recipients

In hematopoietic stem cell transplant (HSCT) recipients the recognition of polymorphic antigens by the donor-derived immune system is an important mechanism underlying both graft-versus-host disease (GvHD) and graft-versus leukaemia (GvL) effect. Here we show that a subset of hematopoietic stem cell transplant recipients (13.9 %, n=108) have antibodies directed to surface molecules of dendritic cells. We have used one such serum in conjunction with retroviral expression cloning to identify the highly polymorphic surface molecule immunoglobulin-like transcript 5 (ILT5) as one of the targets of DCreactive antibodies. ILT5 reactive antibodies were found in 5.4 % of HSCT patients but not in solid organ transplant recipients, patients with collagen diseases, multiparous women, polytransfused or healthy individuals. We show that ILT5 specific antibodies can mediate killing of ILT5-bearing cells and furthermore demonstrate ILT5 expression in some leukemic cells indicating that it might be a target for GvL effects. Thus, our results represent the first description of potent allogeneic antibody responses to a non-MHC cell surface molecule in hematopoietic stem cell transplanted patients and warrant further studies to elucidate the role of antibodies to polymorphic cell surface molecules in GvL and GvH responses. For personal use only. on August 31, 2017. by guest www.bloodjournal.org From