Multiple transcripts of the killer cell immunoglobulin-like receptor family, KIR3DL1 (NKB1), are expressed by natural killer cells of a single individual

Natural killer (NK) cells express receptors that are ligands for HLA class I molecules. One family of such NK receptors are called killer cell immunoglobulin-like receptors (KIR). The KIR2DL (inhibiting) and KIR2DS (activating) molecules recognize HLA-Cw antigens, while the KIR3DL (inhibiting) and KIR3DS (activating) molecules interact with HLA-B antigens with the Bw4 epitope. No NK receptors have yet been identified for HLA-B antigens with the Bw6 epitope. We here report four novel full length cDNA transcripts encoding KIR3DL1-like proteins isolated from mRNA obtained from interleukin-2-activated peripheral blood mononuclear cells of a donor with two HLA-B antigens expressing the Bw6 epitope. These four transcripts belong to a group of closely related KIR3DL1-like molecules initially defined by the cDNA clone NKB1. They differ from NKB1 by only 2 to 7 nucleotides and have 2 to 4 codon changes within the 423 residues of the mature protein. All transcripts were detected by RT-PCR, together with the previously reported KIR3DL1 transcripts, NKB1 and KIR3DL1v, in mRNA from NK cells of 10 of 10 donors tested, and in seven of eight NK clones derived from one donor. Functionally, the KIR3DL1 receptors expressed by five DX9-positive NK clones were not inhibiting NK-mediated cytotoxicity when tested against the 721.221 B-lymphoblastoid cell line expressing a HLA-B antigen with Bw4 epitope. All NK clones were, however, inhibited by 721.221 cells transfected with a HLA-B antigen carrying the Bw6 epitope.