title: Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor.
abstract: Killer Ig-like receptors (KIR) and HLA class I ligands were studied in unrelated hemopoietic stem cell transplantation for chronic myeloid leukemia (n = 108). Significantly improved overall survival was observed in patients, which were homozygous for HLA-C-encoded group 1 (C1) ligands compared with those with group 2 (C2) ligands. Favorable outcome in the former patient group was an early effect that was highly significant in patients transplanted with G-CSF-mobilized peripheral blood and patients with advanced disease stages. In contrast, presence of C1 ligands in the donor was associated with significantly reduced patient survival. The differential roles of the two HLA-C ligands are explained in the context of a biased NK cell reconstitution, which is generally dominated by the presence of C1- but absence of C2-specific NK cells. The clinical observations are corroborated by in vitro experiments showing that NK cells derived from hemopoietic progenitor cells generally acquire the C1-specific inhibitory KIR2DL2/3 at earlier time points and with higher frequency than the C2-specific KIR2DL1. These findings define a novel determinant for understanding the role of NK cells in clinical hemopoietic stem cell transplantation.
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Fischer
authors.forename: Hellmut
authors.initials: H
authors.lastname: Ottinger
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ferencik
authors.forename: Martina
authors.initials: M
authors.lastname: Sribar
authors.forename: Michael
authors.initials: M
authors.lastname: Punzel
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Schwan
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
authors.forename: Peter
authors.initials: P
authors.lastname: Wernet
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D015236:HLA-C Antigens / Q000276:immunology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D015996:Survival Rate; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D016179:Granulocyte Colony-Stimulating Factor