Novel receptor trem (triggering receptor expressed on myeloid cells) and uses thereof

Abstract

Novel activating receptors of the lg super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-β. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

What is claimed is: 
     
         1 . An antibody that is capable of specifically binding a polypeptide comprising amino acids D38-F48 and T70-L96 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         2 . The antibody according to  claim 1 , which is capable of specifically binding a polypeptide comprising amino acids D38-F48 and T70-R84 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         3 . The antibody according to  claim 1 , the epitope of which comprises one, two or all of the amino acid residues selected from the group consisting of D38, K40 and D42 of wild type human TREM-1 and one, two three, four, five, six, seven, eight, nine, ten or all of the amino acid residues selected from the group consisting S74, K75, P79, V80, Q81, V82, G83, Y90, H91, H93 and R97 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         4 . The antibody according to  claim 1 , the epitope of which comprises one, two or all of the amino acid residues selected from the group consisting of D38, K40 and D42 of wild type human TREM-1 and one, two three, four, five, six or all of the amino acid residues selected from the group consisting K75, V80, Q81, Y90, H91, H93 and R97 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         5 . The antibody according to  claim 1 , which has an epitope comprising one, two or all of the amino acid residues selected from the group consisting of D38, K40 and D42 of wild type human TREM-1 and one, two three, four or all of the amino acid residues selected from the group consisting of K75, Y90, H91, H93 and R97 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         6 . The antibody according to  claim 1 , which has an epitope comprising the amino acid residues D38, K40, K75, Y90, H91 and R97 of wild type human TREM-1 (SEQ ID NO: 3). 
     
     
         7 . The antibody according to  claim 1 , which has an epitope comprising the amino acid residues D38, K40, Y90, H91 and R97 of wild type human TREM-1 (SEQ ID NO: 3).