Synthesis and immunostimulatory activity of TLR7 ligand conjugate

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  • TLR7リガンド複合体の合成と免疫増強活性

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Abstract

<p> Toll-like receptors (TLRs) are transmembrane proteins classified into pattern recognition receptors (PRRs). TLRs are found in cell surface and/or endocytic vehicles in immune cells. TLRs activate innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) derived from bacteria and viruses and damage-associated molecular patterns (DAMPs) produced by damaged tissue. The activation of innate immunity induces adaptive immunity that plays an important role in the host defense against pathogenic infection. On the other hand, abnormal activation of innate immunity causes immune disorders such as autoimmune disease. Therefore, TLRs are important molecules in the immune system. So far, 10 types of TLRs (TLR1 to TLR10) in humans and 12 types of TLRs (TLR1 to TLR9, TLR11 to TLR13) in mice have been found. TLR1, TLR2, TLR4, and TLR6 are found on the cell surface, and TLR3, TLR7, TLR8, and TLR9 are found in the endosomal compartment. Each TLR recognizes specific PAMPs and DAMPs ; lipopeptides for TLR1/2 and TLR2/6 ; nucleic acid structures for TLR3, TLR7, TLR8 and TLR9 ; lipopolysaccharide (LPS) structures and heat-shock proteins for TLR4. In recent years, various ligands activating TLRs signal have also been chemically synthesized and have been utilized as effective adjuvants in antiviral and anticancer therapy. Regarding TLR7 ligand (TLR7L), conjugates with peptides, polymers, proteins, glycans, and nanoparticles have attracted much attention because they have great potencies on the humoral and cellular immune response. In this paper, we describe recent progress in the synthesis and biological property of TLR7 ligand conjugate containing our recent study.</p>

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