title: Minor histocompatibility antigen UTY as target for graft-versus-leukemia and graft-versus-haematopoiesis in the canine model.
abstract: Male patients with female-stem-cell donors have better prognosis compared to female-to-male combinations due to Y-encoded minor histocompatibility antigens recognized by female-alloimmune-effector lymphocytes in the context of a graft-versus-leukemia (GvL) effect. We provide data in a dog-model that the minor histocompatibility antigen UTY might be a promising target to further improve GvL-immune reactions after allogeneic-stem-cell transplantations. Female-canine-UTY-specific T cells (CTLs) were stimulated in vitro using autologous-DCs loaded with three HLA-A2-restricted-UTY-derived peptides (3-fold-expansion), and specific T cell responses were determined in 3/6 female dogs. CTLs specifically recognized/lysed autologous-female-peptide-loaded DCs, but not naïve-autologous-female DCs and monocytes. They mainly recognized bone-marrow (BM) and to a lower extent DCs, monocytes, PBMCs and B-cells from DLA-identical-male littermates and peptide-loaded T2-cells in an MHC-I-restricted manner. A UTY-/male-specific reactivity was also obtained in vivo after stimulation of a female dog with DLA-identical-male PBMCs. In summary, we demonstrated natural UTY processing and presentation in dogs. We showed that female-dog CTLs were specifically stimulated by HLA-A2-restricted-UTY peptides, thereby enabling recognition of DLA-identical-male cells, mainly BM cells. These observations suggest UTY as a promising candidate-antigen to improve GvL-reactions in the course of immunotherapy.
authors.affiliation: Medical Department III, University Hospital Großhadern, Ludwig-Maximilians-University, Munich, Germany. dagmar_bund@gmx.de
authors.forename: D
authors.initials: D
authors.lastname: Bund
authors.forename: R
authors.initials: R
authors.lastname: Buhmann
authors.forename: F
authors.initials: F
authors.lastname: Gökmen
authors.forename: J
authors.initials: J
authors.lastname: Zorn
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: H M
authors.initials: HM
authors.lastname: Schmetzer
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D020544:Graft vs Leukemia Effect / Q000187:drug effects / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D008297:Male; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D006182:H-Y Antigen