title: The reactivity of Bw4+ HLA-B and HLA-A alleles with KIR3DL1: implications for patient and donor suitability for haploidentical stem cell transplantations.
abstract: Natural killer (NK)-cell alloreactivity can be exploited in haploidentical hematopoietic stem cell transplantation (HSCT). NK cells from donors whose HLA type includes Bw4, a public epitope present on a subset of HLA-B alleles, can be alloreactive toward recipients whose cells lack Bw4. Serologically detectable epitopes related to Bw4 also exist on a subset of HLA-A alleles, but the interaction of these alleles with KIR3DL1 is controversial. We therefore undertook a systematic analysis of the ability of most common HLA-B alleles and HLA-A alleles with Bw4 serologic reactivity to protect target cells from lysis by KIR3DL1-dependent NK cells. All Bw4(-) HLA-B alleles failed to protect target cells from lysis. All Bw4(+) HLA-B alleles with the exception of HLA-B*1301 and -B*1302 protected targets from lysis. HLA-A*2402 and HLA-A*3201 unequivocally protected target cells from lysis, whereas HLA-A*2501 and HLA-A*2301 provided only weak protection from lysis. KIR3DL1-dependent alloreactive NK clones were identified in donors with HLA-A*2402 but not in donors with HLA-B*1301 or -B*1302. These findings clarify the HLA types that donors and recipients need in haploidentical HSCT and other NK allotherapies in order to benefit from NK alloreactivity.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia.
authors.forename: Bree A
authors.initials: BA
authors.lastname: Foley
authors.forename: Dianne
authors.initials: D
authors.lastname: De Santis
authors.forename: Els
authors.initials: E
authors.lastname: Van Beelen
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Lathbury
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
authors.forename: Campbell S
authors.initials: CS
authors.lastname: Witt
mesh_terms: D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D054341:Receptors, KIR3DL1 / Q000276:immunology*; D014181:Transplantation Immunology
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1