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 Blood, 1 August 2008, Vol. 112, No. 3, pp. 708-710.
Prepublished online as a Blood First Edition Paper on May 23, 2008; DOI 10.1182/blood-2008-02-137521.

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Submitted February 4, 2008
Accepted April 16, 2008

Human leukocyte antigens A23, A24 and A32 but not A25 are ligands for KIR3DL1

Martin Stern*, Loredana Ruggeri, Marusca Capanni, Antonella Mancusi, and Andrea Velardi

Department of Hematology, University Hospital Basel, Basel, Switzerland
Division of Hematology & Clinical Immunology, University of Perugia, Perugia, Italy

* Corresponding author; email: sternm{at}uhbs.ch.

Inhibitory killer cell immunoglobulin receptors (KIR) bind to MHC antigens. Concise knowledge KIR ligands allows prediction of NK alloreactivity after hematopoietic stem cell transplantation (HSCT). KIR3DL1 binds to the Bw4 epitope on HLA-B antigens. While the same epitope is also found on four 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 serological 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 HSCT.


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