LINDELL BEACH, B.C. — Scientists at the Scripps Research Institute in California have been studying a unique family of cow antibodies that offer potential for developing new human medicine.
These antibodies are large proteins that have a tail and identical arms like lobsters. They use these arms for grabbing bacteria or viruses. The part that does the grabbing is a cluster of protein loops called complementarity-determining regions (CDRs) and are unusually long.
By modifying the genes that generate the CDRs, the cow’s immune system can be improved to generate a variety of antibodies that can attach to a greater number of pathogens.
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Scientists have known for a while that cows have unusually long CDRs in a particular region known as CDR H3. However, their potential has remained largely unknown until recently.
“There were a few papers in the literature over the last 15 or so years showing that cows had unusually long CDR3s, but not a lot of work has been done in this area,” said professor Vaughn V. Smider, assistant professor of cell and molecular biology at Scripps.
What has excited researchers is that these unusually long CDRs might be the key to the immunity’s defence against serious infection, even HIV.
A study reported in the journal Nature in August 2012 stated that the institute’s scientists had isolated an anti-HIV antibody with a long CDR H3 region that enabled it to crab the virus’s structure and neutralize the infectivity of most HIV strains.
“Long CRD3s are known to be important in fighting off HIV infection,” said Smider.
“We are investigating whether cows might be able to make potent anti-HIV antibodies. Cows appear to have a unique mechanism that can efficiently mutate the CDR3s to give them new structures and binding specificities.”
While cows have the ability to make long CDR3s at will, it is rare in humans. The benefit is that these long antibodies can probe cellular crevices to reach and bind onto a hidden bacterium that would normally be out of reach to conventional antibodies.
“It looks like a ball on a stick and protrudes out from the antibody surface to bind antigens,” Smider said.
This unique ability could be linked to cows’ four-chamber stomach.
“So far, cows are unique in having these long CDR3s,” he said.
“We have suggested that the four-chambered stomach, and particularly the rumen, might provide a unique antigen load on the immune system. If some of these bacteria escape from the stomach and get into the blood stream or other tissues, there could be some pretty serious infections. This may have led to the unusual antibody structure.”
Researchers have carried out a structural analysis of cow antibodies and found them unique with a long stalk on the top of which was the antigen-binding knob. That knob was formed by an amino acid that contained sulfur. This form of amino acid, called a cysteine, will bond to another cysteine on the same protein chain to form a loop. These loops are what grab the antigens.
“Disulfide bonds create unique loops for antigen binding,” said Smider.
As unique as they are to cows, other animal species could have something similar but be yet undiscovered, he said.
The focus is now to develop biomedical human and veterinary applications.
