A NOVEL PAIR OF IMMUNOGLOBULIN-LIKE RECEPTORS EXPRESSED BY B-CELLS AND MYELOID CELLS

An Fc alpha receptor probe of human origin was used to identify novel members of the Ig gene superfamily in mice, Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDN As isolated from a mouse splenic library, Both type I transmembrane pr oteins possess similar ectodomains with six Ig-like loops, but have di fferent transmembrane and cytoplasmic regions, The predicted PIR-A pro tein has a short cytoplasmic tail and a charged Arg residue in the tra nsmembrane region that, by analogy with the FccuR relative, suggests t he potential for association with an additional transmembrane protein to form a signal transducing unit. In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containi ng four potential immunoreceptor tyrosine-based inhibitory motifs. The se features are shared by the related killer inhibitory receptors, PIR -A proteins appear to be highly variable, in that predicted peptide se quences differ for seven randomly selected PIR-A clones, whereas PIR-B cDNA clones are invariant, Southern blot analysis with PIR-B and PIR- A-specific probes suggests only one PIR-B gene and multiple PIR-A gene s. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloi d lineage cells, wherein both are expressed simultaneously, The charac teristics of the highly-conserved PIR-A and PIR-B genes and their coor dinate cellular expression suggest a potential regulatory role in humo ral, inflammatory, and allergic responses.