Diversity of the repertoire of p58 killer cell inhibitory receptors in a single individual

Abstract

p58 Killer cell inhibitory receptors (KIRs) recognize HLA-C molecules on target cell surface and transmit an inhibitory signal to prevent cell-mediated cytotoxicity. p58 KIR family is composed of multiple receptors whose amino acid sequences are similar but their ligand specificity is different. However, it is not clear how diverse the repertoire of p58 KIR is, particularly in a single individual. To address this question, cDNAs were cloned encoding the extracellular domain of p58 KIR from a single individual. Twelve different p58 KIRs were identified suggesting that the repertoire in a single individual is highly diverse. Interestingly, seven of them have hybrid sequences of three previously reported p58 KIRs. Using an RNase protection assay, it was demonstrated that the mRNA transcripts of the hybrid KIRs are present in peripheral blood mononuclear cells (PBMCs). Four differently spliced forms of p58 KIR were also identified indicating that the repertoire is diverse in size as well as in sequence. Putative splicing sites found in p58 KIR cDNAs suggest that the differently spliced forms are produced by alternative splicing mechanism, and that the hybrid KIRs may also be generated by alternative splicing of two consecutive genes and/or by trans-splicing mechanism found in Ig genes in B cells.