KIR2DL5, a novel killer-cell receptor with a D0-D2 configuration of Ig-like domains

Four novel killer-cell Ig-like receptor (KIR) genes were discovered by anal ysis of genomic DNA from a human donor. One gene, KIR2DL5, is expressed by subpopulations of Mt cells and T cells, whereas expression of the other thr ee genes could not be detected. KIR2DL5 has two extracellular Ig-like domai ns of the DO and D2 type, a structural configuration that was previously un ique to KIR2DL4. Although having a similar structure overall, the KLR2DL4 a nd KIR2DL5 receptors have distinctive amino acid sequences in the ligand-bi nding extracellular domains and differ in the transmembrane and cytoplasmic motifs that determine signal transduction, Whereas the KIR2DL4 gene is pre sent on all I(IR haplotypes and is expressed by all human NK cells, the KTR 2DL5 gene is restricted to the "B" subset of KIR haplotypes and is clonally expressed by NK cells within an individual. Chimpanzee genes for KIR2DL4 a nd KIR2DL5 have been defined and are very similar in sequence to their huma n orthologs, The donor in whom KIR2DL5 was first detected bears two variant s of it that differ by five nucleotide substitutions in the coding region. Although the substitutions are not predicted to affect gene expression, tra nscription of only one of the two KIR2DL5 variants could be detected.