Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Unusual Antibodies in Cows Suggest New Ways to Make Therapies for People

Published: Monday, June 10, 2013
Last Updated: Thursday, June 13, 2013
Bookmark and Share
Researchers have examined the immune system of cows and found an extraordinary family of antibodies that may benefit humans.

Humans have been raising cows for their meat, hides and milk for millennia. Now it appears that the cow immune system also has something to offer. A study of an extraordinary family of cow antibodies, led by researchers at The Scripps Research Institute (TSRI) and coauthored by three investigators from Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), points to new ways to make human medicines.

The CVM's faculty members' expertise in immunology and infectious disease, as well as their easy access to a herd of cattle, made them a natural fit as collaborators.

"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 in the June 6, 2013 issue of the journal Cell.

Antibodies, large proteins in the immune system, resemble lobsters with a tail and two identical arms for grabbing specific targets, called "antigens," often parts of pathogens like bacteria or viruses. At the end of each arm is a small set of protein loops called complementarity-determining regions (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 foreign invader.

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 defense against a dangerous infection, such as HIV.

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.

As Smider's area of research includes finding new ways to generate therapeutic antibody proteins, reports of long CDR H3 use caught his interest. "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.

Although the structure of the long CDR H3 protein in previous studies of the human anti-HIV antibody had seemed unusual, the corresponding structure in the cow antibodies turned out to be unique in the known world of animal antibodies: a long "stalk" element topped by an antigen-binding "knob." Sequencing of the DNA that codes for the knob region revealed an unusual abundance of cysteine-a sulfur-containing amino acid that is apt to bond to a nearby cysteine on the same protein chain, thus forming a loop.

Analyses of these DNA sequences, some of which were conducted at Texas A&M, also indicated that, in the cow B-cells where these antibodies are made, the knob-coding gene segments are extraordinarily likely to develop point mutations that either add or subtract cysteines. The effect of these tiny mutations is to create or remove-often radically-antigen-grabbing loops on the structure.

In the cows, binding of these antibodies to viruses is almost entirely done by the knob on the long CDR H3, which shows that these antibodies do have an important function in the immune system. "For the very first time we have an ultra-long CDR3 antibody binding to an actual pathogen," said Mwangi, an expert in immunology who completed the initial assays that determined the binding target for these antibodies.

One question that remains is why the cow immune system evolved to make such antibodies. Smider suspects that it has to do with cows' unusual, four-chambered, grass-fermenting stomach, with its extensive collection of bacteria and other microorganisms. "If some of these escape from the stomach and get into the bloodstream or other tissues, there could be some pretty serious infections; so that's our starting hypothesis for why cows have this unusual immune defense," he said.

The stalk-and-knob structure of the CDR H3 loops on these antibodies, which resemble structures found in some insect poisons and other proteins, also suggest that they evolved to grab a particular type of target. "What comes to mind are ion channel or pore structures in the walls of cells," Smider said. "In any case, we're hoping to find out whether any of the structures targeted by these knobs exist on microorganisms that cause human disease."

"Potentially, the outcome of this research is going to be huge," Mwangi said, "not only for cattle but also for human health."

Michael F. Criscitiello, Assistant Professor at the CVM and one of the study's authors, said this was a wonderful chance to contribute to such a groundbreaking study, as researchers at the CVM had experience with-and access to-cows. The entire project was made possible through collaborations of various people and labs each contributing their expertise to add pieces to the puzzle.

"Such collaborations bring together specialists in diverse fields and certainly facilitate future research," said Terje Raudsepp, Associate Professor at the CVM and another of the study's authors. "This is expected to lead to new collaborative projects in the future."

The study was supported by the American Cancer Society, National Institutes of Health, Skaggs Institute for Chemical Biology,Scripps Translational Science Institute, Texas A&M College of Veterinary Medicine & Biomedical Sciences, and United States Department of Agriculture.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

When It Comes to Genetic Code, Optimum Isn't Always Best
Imagine two steel springs identical in look and composition but that perform differently because each was tempered at a different rate.
Friday, February 22, 2013
Scientific News
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Faster, Cheaper Way to Produce New Antibiotics
A novel way of synthesising a promising new antibiotic has been identified by scientists at the University of Bristol.
Process Contaminants in Vegetable Oils and Foods
Glycerol-based process contaminants found in palm oil, but also in other vegetable oils, margarines and some processed foods, raise potential health concerns for average consumers of these foods in all young age groups, and for high consumers in all age groups.
Improving Natural Killer Cancer Therapy
Vanderbilt University researchers discover transcription factor critical for NK cell expansion. Findings could lead to increased therapeutic efficacy.
Molecular Mechanism For Generating Specific Antibody Responses Discovered
Study could spur more ways to treat autoimmune disease, develop accurate vaccines.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
It’s Now Easier To Go With The Flow
Rice University tool simplifies comparison of flow cytometry data for laboratories.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
Genetic Variant May Help Explain Why Labradors Are Prone To Obesity
A genetic variation associated with obesity and appetite in Labrador retrievers – the UK and US’s favourite dog breed – has been identified by scientists at the University of Cambridge. The finding may explain why Labrador retrievers are more likely to become obese than dogs of other breeds.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!