KLH
Applications
Keyhole limpet hemocyanin (KLH) is a highly potent T-cell dependent immunostimulatory protein and adjuvant. The molecule has an extensive history of safe and effective use in humans for vaccine development and immunological research. As an essential carrier protein for the rapidly developing field of synthetic conjugate vaccines, KLH has proven to be superior at conferring antigenicity to a wide variety of molecular conjugates and has enabled a broad array of new vaccines and active immunotherapies.
The potent immunogenicity and excellent safety record of KLH also makes it an excellent choice for immunological research applications, including:
- Antibody Generation - KLH is an effective carrier protein for poorly antigenic molecules in most species. Immunoconjugates of KLH are routinely used to generate antibodies against small molecules, polysaccharides, and other poorly antigenic molecules in mice, rats, chickens, rabbits, goats, swine, and horses.
- Immune Response Testing - KLH is widely used as a neoantigen to assess functional primary immune response and immunocompetence in clinical settings involving immunosuppression such as transplantation and HIV infection. KLH is also used to monitor immune responses in patients receiving therapeutic cancer vaccines and other immunotherapies.
- Immunotoxicology - KLH immunization and ELISA testing of antibody response are rapidly replacing the traditional sheep red blood cell (SRBC) antigen and plaque-forming assay for T-cell dependent antigen response (TDAR) immunotoxicity testing of new drugs. KLH's advantages include ease of use, greater reliability, and better standardization relative to SRBC assays.
Molecular Properties
KLH is the high molecular mass respiratory glycoprotein from the hemolymph of the marine mollusc Megathura crenulata. The KLH protein is a T-cell dependent antigen. The large size of the KLH protein, which has a monomer molecular mass of 360-390 kD and a native didecamer mass of ~8,000 kD, contributes to efficient endocytosis by antigen presenting cells (APCs), wherein it is processed into peptides, bound to MHC class II molecules, and presented to the immune system on the APC surface membrane. APC presentation of antigenic peptides in the context of MHC class II initiates the binding, priming and proliferation of CD4+ T helper cells, driving T cell lymphokine secretion and a cascade of cellular and humoral responses. KLH is highly glycosylated, and a significant component of the molecule's immunogenicity is attributed to the presence of unusual carbohydrate moieties, including unique Gal-(beta1-6)Man-, Gal(beta1-4)Fuc-, and Gal(beta1-4)Gal(beta(1-4)Fuc- structural motifs on N-glycans.
Courtesy of Z. Zhu, Center for Integrative Molecular Biosciences and Dept. of Cell Biology, Scripps Research Institute, La Jolla, CA.
Courtesy of Z. Zhu, Center for Integrative Molecular Biosciences and Dept. of Cell Biology, Scripps Research Institute, La Jolla, CA.