title: Human leukocyte antigens A23, A24, and A32 but not A25 are ligands for KIR3DL1.
abstract: Inhibitory killer cell immunoglobulin receptors (KIR) bind to major histocompatibility complex antigens. Concise knowledge of KIR ligands allows prediction of natural killer (NK)-cell alloreactivity after hematopoietic stem cell transplantation. KIR3DL1 binds to the Bw4 epitope on HLA-B antigens. Although the same epitope is also found on 4 HLA-A antigens (HLA-A23/24/25/32), these are not currently regarded as KIR3DL1 ligands. We show that expression of HLA A*2301, A*2402, or A*3201 but not HLA A*2501 protects target cells from lysis by KIR3DL1(+) NK cells. KIR3DL1(+) NK cells from donors expressing the Bw4 epitope on an HLA-A antigen only are fully functional and capable of lysing Bw4(-) target cells. HLA A25 differs at amino acid 90, close to the serologic Bw4 epitope, from A23/24/32 and from Bw4(+) HLA-B antigens. These data suggest that HLA-A antigens should be taken into consideration when assessing the potential for NK alloreactivity after hematopoietic stem cell transplantation.
authors.affiliation: Department of Hematology, University Hospital Basel, Basel, Switzerland. sternm@uhbs.ch
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Marusca
authors.initials: M
authors.lastname: Capanni
authors.forename: Antonella
authors.initials: A
authors.lastname: Mancusi
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
mesh_terms: D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000378:metabolism*; D059871:HLA-A24 Antigen; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D054341:Receptors, KIR3DL1 / Q000378:metabolism*; D014181:Transplantation Immunology
chemical_list: D015234:HLA-A Antigens; C084028:HLA-A*23 antigen; C037019:HLA-A*25 antigen; C531148:HLA-A*32 antigen; D059871:HLA-A24 Antigen; D008024:Ligands; D054341:Receptors, KIR3DL1