ANALYSIS OF IGA NETWORK BY GENE TARGETING

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We hae found a novel murine cell-surface glycoprotein, designated as q91, expressed mainly in myeloid cells such as macrophages and mast cells. The molecule has six immunoglobulin-line extracellular domains, a transmembrane segment, and a cytoplasmic tail containing four immunoreceptor tyrosine-based inhibition motif (ITIM) or ITIM-like sequences, resembling the structural features of human killer-cell inhibitory receptors (KIR). p91 comprises a polymorphic gene family, harboring one potent inhibitory-type p91 and at least two other p91 genes.Tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching each of the third ITIM and the fourth ITIM-like sequences found in the cytoplasmic portion of p91A,the sole inhibitory-type p91, associated with the tyrosine phosphatases SHP-1 and SHP-2. In addition, the phosphotyrosyl peptide matching the third ITIM sequence also bound the inositol 5-phosphatase SHIP.Thses results support the notion that p91A may function as an inhibitory cell-surface molecule against cell activation. The p91 genes were shown to be clustered in the proximal region of mouse chromosome 7, a syntenic position of human chromosome 19 where the genes for the KIR family are found. A human cDNA clone cross-hybridizing to a murine p91 probe was isolated from a human spleen cDNA library, and was found to be coding for a molecule quits similar to members of the immunoglobulin-like transcript (or ILT) family. The gene was found to locate on human chromosome 19q13.3-13.4. These results will establish the existence of a novel set of potent regulatory receptors in mouse and man, similar but different from the KIR family.