title: Allogeneic disparities in immunoglobulin-like transcript 5 induce potent antibody responses in hematopoietic stem cell transplant recipients.
abstract: 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 and graft-versus-leukemia (GVL) effect. Here we show that a subset of HSCT 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 dendritic cell-reactive antibodies. ILT5 reactive antibodies were found in 5.4% of HSCT patients but not in solid organ transplantation recipients, patients with collagen diseases, multiparous women, or polytransfused or healthy persons. 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-major histocompatibility complex 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 graft-versus-host responses.
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfistershammer
authors.forename: Anita
authors.initials: A
authors.lastname: Lawitschka
authors.forename: Christoph
authors.initials: C
authors.lastname: Klauser
authors.forename: Judith
authors.initials: J
authors.lastname: Leitner
authors.forename: Roman
authors.initials: R
authors.lastname: Weigl
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
authors.forename: Otto
authors.initials: O
authors.lastname: Majdic
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: Gottfried F
authors.initials: GF
authors.lastname: Fischer
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D003095:Collagen Diseases / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D051379:Mice; D010298:Parity / Q000276:immunology; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000276:immunology*; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D007518:Isoantibodies; C527699:LILRB3 protein, human; D011971:Receptors, Immunologic