Activating and inhibitory nature of the murine paired immunoglobulin-like receptor family.
Clones for murine paired immunoglobulin-like receptors (PIR) were first isolated as those coding for type I transmembrane glycoproteins with six immunoglobulin-like domains homologous to human Fc alphaR, bovine Fc gamma2R, and other related receptors. However, they turned out to bind neither IgA nor other immunoglobulins in the case of the ectopic expression on COS-1 fibroblastic cells. PIR-A and B are expressed on a wide variety of cells in the murine immune system, such as in B cells, mast cells, macrophages, and dendritic cells, mostly in a pairwise fashion. PIR-A requires homodimeric Fc receptor common gamma chain, which harbors an immunoreceptor tyrosine-based activation motif, for its efficient cell surface expression and for the delivery of activation signaling. In contrast, PIR-B contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic portion and inhibits receptor-mediated activation signaling in vitro upon engagement with other activating-type receptors such as the antigen receptor on B cells and the high affinity Fc receptor for IgE on mast cells. ITIMs of PIR-B on macrophages and B cells have been shown to be constitutively phosphorylated in their tyrosine residues. Although the ligand for PIR still remains unknown, the transgenics and the gene-targeted mice will provide us with valuable information on their physiological roles in the immune regulation.
Takai
T
T
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. tostakai@idac.tohoku.ac.jp
Ono
M
M
D000818:Animals; D005075:Biological Evolution; D002417:Cattle; D002874:Chromosome Mapping; D015870:Gene Expression; D006801:Humans; D051379:Mice; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C105948:Pira1 protein, mouse; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic