GENOMIC STRUCTURE OF PIR-B, THE INHIBITORY MEMBER OF THE PAIRED IMMUNOGLOBULIN-LIKE RECEPTOR GENES IN MICE

The genes encoding the murine paired immunoglobulin-like receptors PIR -A and PIR-B are members of a novel gene family which encode cell-surf ace receptors bearing immunoreceptor tyrosine based inhibitory motifs (ITIMs) and their non-inhibitory/activatory counterparts. PIR-A and PI R-B have highly homologous extracellular domains hut distinct trans me mbrane and cytoplasmic regions A charged arginine in the transmembrane region of PIR-A suggests its potential association with other trans m embrane proteins to form a signal transducing unit. PIR-B, in contrast , has an uncharged transmembrane region and several ITIMs in its cytop lasmic tail. These characteristics suggest that PIR-A and PIR-B which are coordinately expressed by B cells and myeloid cells, serve counter -regulatory roles in humoral and inflammatory responses. In the presen t study we have determined the genomic structure of the single copy PI R-B gene. The gene consists of 15 exons and spans approximately 8 kilo bases. The first exon contains the 5' untranslated region, the ATG tra nslation start site, and approximately half of the leader peptide sequ ence. The remainder oi the leader peptide sequence is encoded by exon 2. Exons 3-8 encode the six extracellular immunoglobulin-like domains and exons 9 and 10 code for the extracellular membrane proximal and tr ansmembrane regions. The final five exons (exons 11-15) encode for the ITIM-bearing cytoplasmic tail and the 3' untranslated region. The int ron/exon boundaries of PIR-B obey the GT-AG rule and are in phase I, w ith the notable exception of the three boundaries determined for ITIM- containing exons. A microsatellite composed of the trinucleotide repea t AAG in the intron between exons 9 and 10 provides a useful marker fo r studying population genetics.