Abstract: Compositions and methods of use thereof for modulating FLRT3 mediated signaling are provided. For example, immunomodulatory agents are provided that reduce FLRT3 expression, ligand binding, crosslinking, FLRT3 mediated signaling, or a combination thereof. In another embodiment, immunomodulatory agents are provided that enhance or promote FLRT3 expression, ligand binding, crosslinking, FLRT3 mediated signaling, or a combination thereof. Such agents can be used to modulate an immune response in a subject in need thereof.

Abstract: Compositions and methods of use thereof for modulating LAIR-1 are provided. For example, immunomodulatory agents are provided that reduce LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Exemplary agents include (i) a soluble LAIR-2 polypeptide or fusion protein, (ii) a soluble LAIR-1 polypeptide or fusion protein, (iii) a function blocking anti-LAIR-1 antibody, (iv) an antibody that depletes LAIR-1 positive cells, and (y) combinations thereof. Immunomodulatory agents are also provided that increase LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof. Exemplary agents include: (i) a function activating anti-LAIR-1 antibody, (ii) a function blocking anti-LAIR-2 antibody, and (iii) a combination thereof.

Abstract: Compositions and methods of use thereof for modulating B7-H4 are provided. For example, immunomodulatory agents are provided that reduce B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Immunomodulatory agents are also provided that increase B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof.

Abstract: Compositions that bind to killer cell lectin-like receptor G1 (KLRG1) or its ligands are provided. The compositions can agonize or antagonize signal transduction through KLRG1. For example, some compositions either inhibit or block signal transduction through KLRG1 while other compositions induce or enhance signal transduction through KLRG1. In some embodiments, the compositions are anti-KLRG1 antibodies, KLRG1 fusion proteins, or KLRG1 ligand fusion proteins. One embodiment provides antibodies and antigen binding fragments thereof that immuno specifically bind KLRG1 and block, inhibit or reduce signal transduction through KLRG1. In another embodiment, the antibodies specifically bind to human KLRG1 under physiological conditions.