Unusual antibodies in cows point to ways of developing medicines for people

A study led by scientists from The Scripps Research Institute, focusing on an extraordinary family of cow antibodies, points to new ways to make human medicines.

An account of the research can be found here at Science Daily.

“These antibodies’ structure and their mechanism for creating diversity haven’t been seen before in other animals’ antibodies,” said Vaughn V. Smider, assistant professor of cell and molecular biology at TSRI and principal investigator for the study, which appears as the cover story in the June 6, 2013 issue of the journal Cell.

ScienceDaily describes antibodies, part of our immune system, as large proteins that resemble lobsters with a tail and two identical arms for grabbing specific targets (called “antigens,” often parts of bacteria or viruses).

At the business end of each arm is a small set of protein loops called complementarity-determining regions (or CDRs), which actually do the grabbing.

By rearranging and mutating the genes that code for CDRs, an animal’s immune system can generate a vast and diverse population of antibodies which collectively can bind to just about any of the body’s foreign invaders.

In humans and in many other mammals, most of an antibody’s specificity for a target is governed by the largest CDR region, CDR H3.

Researchers have been finding hints that an unusually long version of this domain can sometimes be the key to a successful defence against a dangerous infection.

In a study reported in Nature last August, for example, Ian A. Wilson, who is Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and collaborators isolated an anti-HIV antibody with a long CDR H3 region — twice normal length — which allows it to grab a crucial structure on the virus and thereby neutralise the infectivity of most HIV strains.

Waithaka Mwangi, assistant professor in the Texas A&M College of Veterinary Medicine and Biomedical Sciences (CVM) and an author on the Cell paper, suggests thinking of these long CDRs as a probe on a thin extended scaffold that can fit narrow crevices to reach and bind unique hidden pathogen determinants that ordinary antibodies cannot.

Reports on these antibodies recently caught the interest of Smider, whose area of research includes finding new ways to generate therapeutic antibody proteins.

“We started thinking about how we could make these long CDR3s that are so rare in humans, and we knew from the literature that cows make even longer ones all the time,” he said.

The research team performed a detailed structural and sequence analysis of these unusually long CDR H3 cow antibodies, to gain insight into how they are made naturally and how such structures might be engineered in the laboratory.

One question that remains is why the cow immune system evolved to make such antibodies.

Smider and his colleagues hope to harness the potential power of long CDR H3 antibodies for a wide variety of human — and perhaps also veterinary — medical applications.


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