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Bund, D. ; Buhmann, R. ; Gökmen, F. ; Zorn, J. ; Kolb, H.-J. ; Schmetzer, H.M.*

Minor histocompatibility antigen UTY as target for graft-versus-leukemia and graft-versus-haematopoiesis in the canine model.

Scand. J. Immunol. 77, 39-53 (2013)
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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 naive-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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cytotoxic T-lymphocytes ; Stem-cell Transplantation ; Restricted Tissue Distribution ; Human Y-chromosome ; Class-i Genes ; Peripheral-blood ; Immunohistochemical Detection ; Progenitor Cells ; Host Disease ; H-y
ISSN (print) / ISBN 0300-9475
e-ISSN 1365-3083
Quellenangaben Band: 77, Heft: 1, Seiten: 39-53 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed