KIR2DL5, a Novel Killer-Cell Receptor with a D0-D2 Configuration of Ig-Like Domains

Abstract

Four novel killer-cell Ig-like receptor (KIR) genes were discovered by analysis of genomic DNA from a human donor. One gene, KIR2DL5, is expressed by subpopulations of NK cells and T cells, whereas expression of the other three genes could not be detected. KIR2DL5 has two extracellular Ig-like domains of the D0 and D2 type, a structural configuration that was previously unique to KIR2DL4. Although having a similar structure overall, the KIR2DL4 and KIR2DL5 receptors have distinctive amino acid sequences in the ligand-binding extracellular domains and differ in the transmembrane and cytoplasmic motifs that determine signal transduction. Whereas the KIR2DL4 gene is present on all KIR haplotypes and is expressed by all human NK cells, the KIR2DL5 gene is restricted to the “B” subset of KIR haplotypes and is clonally expressed by NK cells within an individual. Chimpanzee genes for KIR2DL4 and KIR2DL5 have been defined and are very similar in sequence to their human orthologs. The donor in whom KIR2DL5 was first detected bears two variants of it that differ by five nucleotide substitutions in the coding region. Although the substitutions are not predicted to affect gene expression, transcription of only one of the two KIR2DL5 variants could be detected.

The Repertoire of Killer Cell Ig-Like Receptor and CD94:NKG2A Receptors in T Cells: Clones Sharing Identical αβ TCR Rearrangement Express Highly Diverse Killer Cell Ig-Like Receptor Patterns

“…One possible source of bias is that cells expressing certain combinations of NKR were not captured by the Ab cocktail used in isolating NKR ϩ T cells. This cocktail did not include Abs that bind to either KIR2DL4 or the recently described KIR2DL5 (9,48), and the weak affinity of the CD94-specific Ab for the CD94:NKG2C heterodimer may have meant that this Ab was inefficient in capturing cells via interaction with CD94:NKG2C. A second potential source of bias is that the in vitro cloning procedure did not equally promote the growth of all cells isolated with the Ab cocktail.…”

KIR2DL5 alleles mark certain combination of activating KIR genes

“…Furthermore, eight Hispanic individuals carrying the KIR2DL5 gene were included in the KIR2DL5-sequencing analysis. The DNA samples from blood donors RR and WC in whom the KIR2DL5B*002 and *003 were originally isolated, 5,13 were included as controls for the direct sequencing method.…”

“…4 Despite clustering together into a discrete lineage with high structural homologies, the KIR2DL5 and 2DL4 differ substantially in their amino-acid sequences, genomic locations, population distributions, level of transcriptions, cellsurface expressions, ligand specificities and signaling functions. [5][6][7][8][9] The KIR2DL4 gene is present on most KIR haplotypes and occurs at a frequency of 100% in most populations, whereas KIR2DL5 is variable among KIR haplotypes and thus differs considerably between populations in its frequency. [10][11][12] Two copies of the KIR2DL5 genes have been characterized, KIR2DL5A and KIR2DL5B, that show 99.5-99.7% identity in their coding sequences.…”

Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

“…Over 70 of these KIR profiles have been reported so far in approximately 650 individuals. [11][12][13][14] Aside from subtypes of particular KIR (eg, 2DL5 and 3DL1), all of these putative KIR loci have an expressed product, 11,[15][16][17] thus the KIR genetic profile may be a reflection of the repertoire of KIR available to an individual. We have previously reported the distribution of NK cell receptor repertoires in three distinct populations, Caucasoid, Palestinian and Thai, and observed statistically significant differences in gene frequencies for several of the KIR loci.…”