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A Limited Natural Resource

 

The Giant Keyhole Limpet (Megathura crenulata, source species for KLH protein) is native only to the rocky Pacific Ocean waters off California and Baja.  Its natural habitat is the shallow depths below low tide line.

Precious Cargo on Board

Giant Keyhole Limpet
KLH protein is only found in the hemolymph of the Giant Keyhole Limpet, Megathura crenulata.

KLH produced from sustainable, licensed aquaculture (rather than from small and sensitive wild populations) can protect the precious source species Megathura crenulata and ensure long-term, quality supply of this important biomedical material.

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Vital Tool in Immunology

Keyhole Limpet Hemocyanin (KLH) plays a vital role in immunology and its demand in biopharmaceutical applications is rising rapidly.
The rich blue color of KLH is due to its copper-containing properties.

Aquaculture: The Key to KLH

About KLH

Keyhole limpet hemocyanin (KLH) is a potent, safe immunostimulating protein with an extensive history of use in vaccine development and immunological research. 

This vitally important protein can only be derived from a limited natural resource – the Giant Keyhole Limpet (Megathura crenulata) which naturally lives only in the Pacific coastal waters, from Monterey Bay, California to Isla Asuncion off Baja California, Mexico.

KLH is well known for its potent and safe immune-stimulating properties, with an extensive (50+ years) history of use in immunology....as a vaccine carrier molecule, as a standard assay for measuring humoral and cellular immune function, and as an essential tool for immunotoxicology screening of new drugs.

Biophysical Characteristics

KLH is a very large, high molecular weight, oxygen-carrying metalloprotein from the hemolymph of the marine mollusc Megathura crenulata.

The KLH protein is expressed in two subunit isoforms (KLH1 and KLH2) of approximately 360,000 and 400,000 monomeric molecular weight. The KLH monomers are each composed of 7 or 8 functional unit domains; each functional unit contains an oxygen binding site containing two copper atoms.

Both KLH isoforms assemble into native homo-decamers and -didecamers of 4,000,000 to 8,000,000 molecular weight in hemolymph.

KLH's immunogenicity is partly attributed to the presence of unusual carbohydrate moieties, including unique Fuc(alpha1-3)GalNAc, Gal-(beta1-6)Man-, Gal(beta1-4)Fuc-, and Gal(beta1-4)Gal(beta(1-4)Fuc- structural motifs on N-glycans.(1,2,3)  Terminal mannose residues are mannose receptor ligands and fucose residues are DC-SIGN ligands, suggesting that endocytosis of KLH via C-lectin receptors for antigen presentation in KLH-based conjugate vaccines. KLH has been reported to stimulate dendritic cell maturation from human monocytes in processes possibly involving the mannose receptor.(4)

Size (and Source) Matters
Due to its exceptional size and unusual glycosylation, KLH has not been reproduced synthetically, and is more efficiently and cost-effectively prepared by purification from the hemolymph of the source animal.

Studies have shown that different forms of KLH have distinctly different structural properties and, importantly, may have different inductive effects on the immune system.(5,6,7,8,9,10,11,12,13,20)

Further, studies have reported that the culture, handling and processing of KLH can impact isoform structure and immunogenicity.(14,15,16)

Different forms and supply sources of KLH have been associated with differing magnitudes and variability in IgM and IgG responses.(17,18,19)