C3d of Complement as a Molecular Adjuvant: Bridging Innate and Acquired Immunity

TLDR

The complement system, especially C3, helps the immune system distinguish harmful from harmless antigens by attaching to potential microbial targets. The study aimed to determine whether fusing C3d to an antigen alters acquired immune recognition. Mice were immunized with recombinant hen egg lysozyme fused to murine C3d. HEL fused to two or three copies of C3d was 1,000‑ to 10,000‑fold more immunogenic than HEL alone, demonstrating that C3d acts as a potent molecular adjuvant that profoundly enhances acquired immunity.

Abstract

An optimal immune response should differentiate between harmful and innocuous antigens. Primitive systems of innate immunity, such as the complement system, may play a role in this distinction. When activated, the C3 component of complement attaches to potential antigens on microorganisms. To determine whether this alters acquired immune recognition, mice were immunized with a recombinant model antigen, hen egg lysozyme (HEL), fused to murine C3d. HEL bearing two and three copies of C3d was 1000- and 10,000-fold more immunogenic, respectively, than HEL alone. Thus, C3d is a molecular adjuvant of innate immunity that profoundly influences an acquired immune response.