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

p58 Killer cell inhibitory receptors (KIRs) recognize HLA-C molecules on ta rget cell surface and transmit an inhibitory signal to prevent cell-mediate d cytotoxicity. p58 KIR family is composed of multiple receptors whose amin o acid sequences are similar but their ligand specificity is different. How ever, it is not clear how diverse the repertoire of p58 KIR is, particularl y in a single individual. To address this question, cDNAs were cloned encod ing the extracellular domain of p58 KIR from a single individual. Twelve di fferent p58 KIRs were identified suggesting that the repertoire in a single individual is highly diverse. Interestingly, seven of them have hybrid seq uences of three previously reported p58 KIRs. Using an RNase protection ass ay, it was demonstrated that the mRNA transcripts of the hybrid KIRs are pr esent in peripheral blood mononuclear cells (PBMCs). Four differently splic ed 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 p5 8 KIR cDNAs suggest that the differently spliced forms are produced by alte rnative splicing mechanism, and that the hybrid KIRs may also be generated by alternative splicing of two consecutive genes and/or by trans-splicing m echanism found in Ig genes in B cells. (C) 1999 Elsevier Science B.V. All r ights reserved.