Unusual Antibodies in Cows Suggest New Ways to Make Therapies for People LA JOLLA, CA June 6, 2013 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 new study led by scientists from The Scripps Research Institute (TSRI) focusing on an extraordinary family of cow antibodies points to new ways to make human medicines.
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.
Defense Against Infection
Antibodies, part of our immune system, are 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 defense against a dangerous infection. For example, in a study reported in Nature last August, 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 neutralize 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.
Learning from Nature
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.
To investigate, Smider assembled a collaboration that included the TSRI laboratories of Wilson and Peter G. Schultz, who is the Scripps Family Chair Professor of Chemistry, as well as researchers at CVM. Michael F. Criscitiello, assistant professor at the CVM and a co-author of the paper, embraced the chance to contribute to the groundbreaking study and noted researchers at CVM offered key immunology proficiency with and access to cows. Such collaborations bring together specialists in diverse fields and certainly facilitate future research, added Terje Raudsepp, associate professor at the CVM and another of the study's authors.
The 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.
First author Feng Wang, at the time a postdoctoral research associate with Schultz and Smider at TSRI, led the effort to purify long CDR H3 cow antibodies which represent about 10 percent of the cow antibody repertoire and analyze their corresponding gene sequences. Co-first author Damien C. Ekiert, at the time a graduate student in the Wilson laboratory at TSRI, was able to crystallize the long CDR H3 antibody samples and determine the 3D atomic structures of two representative antibodies by X-ray crystallography.
Although the structure of the long CDR H3 protein in Wilson's 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.
Efficient Way to Evolve
Analyses of these DNA sequences 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. This is a very efficient way to evolve new protein folds, said Wang. Indeed, it seems to be the principal way in which the cow immune system creates a diverse set of these long CDR H3 antibodies.
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.
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 co
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
07/08/2025
July 8 2025, 22:30 (PDT) Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, R...
17/07/2025
Early Thursday morning, the U.S. Senate voted to cut federal funding for PBS and NPR in a bill that also included cuts for foreign aid. In a 51-48 vote, the act...
17/07/2025
GREAT Britain and Northern Ireland Pavilions across IBC2025 (12 15 September, RAI Amsterdam) feature a remarkable 34 companies, each providing unique, innovativ...
17/07/2025
WHITE PLAINS, N.Y. The Society of Motion Picture and Television Engineers today introduced its Content Provenance and Authenticity (CPA) in Media Study Group (S...
17/07/2025
NEW YORK Despite widespread concerns about a soft advertising market, NBCUniversal said it closed its 2025-26 upfront negotiation cycle with a record ad sales v...
17/07/2025
NEW YORK Television advertising remains an effective means to market and influence younger baby boomer and Generation X consumers approaching retirement age, ac...
17/07/2025
ALLENTOWN, Pa. & JERSEY CITY, N.J. Service Electric Cable TV and OpenVault have announced that the operator is deploying the OpenVault Proactive Network Manage...
17/07/2025
WASHINGTON Following up on his first major policy speech just two ago, Federal Communications Commission Chair Brendan Carr is promising to buck the usual summ...
17/07/2025
Luxembourg, 14 July 2025 - SES received the final regulatory approvals for the SES-Intelsat transaction, including the US Federal Communications Commission.
O...
17/07/2025
Berklee Alumni Nominated for 2025 Emmy Awards Twenty-three Berklee alumni received nominations across categories in sound mixing, sound editing, and compositi...
16/07/2025
It's Emmy nominations day, and Sundance Institute storytellers are basking i...
16/07/2025
Spotify's podcast editorial team is always on the hunt for shows and episodes that spark conversation, push boundaries, and keep us coming back for more. As...
16/07/2025
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({...
16/07/2025
Join us at IBC this September and take control of your content. Discover how we're bringing a new level of purpose and precision to the application of AI in...
16/07/2025
Warsaw - Poland, June 24, 2025 - Nielsen, the global leader in audience measurement, data and analytics, has released its latest May All Screens Video Landscape...
16/07/2025
Bluey Tops Nielsen's Overall Streaming List with More Than 25 Billion Minutes Streamed from January through June 2025
Big June Vaults Squid Game into Top O...
16/07/2025
TV SIM, the SBT affiliate serving Esp rito Santo state in Brazil, has launched a transmitter upgrade initiative with the installation of a Rohde & Schwarz R&S T...
16/07/2025
Pebble, the leading automation, content management and integrated channel specialist, is turning its vision to the future of automation with its demonstrations ...
16/07/2025
Ikegami announces a new addition to its UNICAM-XE product range with the introduction of the UHK-X700RF wireless portable camera: The new version has the same f...
16/07/2025
Today, Amazon Web Services added TwelveLabs as a new model provider to Amazon Bedrock, delivering what could be the most significant breakthrough in enterprise ...
16/07/2025
NEW YORK Streaming platforms continued to dominate TV viewing patterns in June, with data from Nielsen's 50th monthly report of The Gauge showing that strea...
16/07/2025
MAHWAH, NJ Ikegami has introduced the the UHK-X700RF wireless portable camera, a new addition to its UNICAM-XE product range with the same feature set, operatio...
16/07/2025
LONDON IBC2025 organizers said global attendees will have access to a new feature that will integrate Amsterdam's GVB public transport pass into the officia...
16/07/2025
July 16th, 2025
Tribeca Films to Release the Acclaimed LARPing Doc WE CAN BE HEROES by Carina Mia Wong and Alex Simmons, Alongside a Slate of Festival-Favori...
16/07/2025
Deltatre Acquires Endeavor Streaming in Major Streaming Industry Move The transaction is expected to close in the third quarter of 2025 By Brandon Costa, Direc...
16/07/2025
SVG Regional Sports Production Summit 2025: All Sessions Now Available to Watch ...
16/07/2025
Wednesday 16 July 2025
Sky and ITV today announced an extension of their long-standing partnership, which will see ITV's content and services remain seamle...
16/07/2025
Sky Sports lifts the lid on Lions life with hilarious behind-the-scenes mockumentaryWednesday 16 July 2025
To view this content, please enable our use of cooki...
16/07/2025
CULVER CITY, CALIFORNIA Apple TV+ today earned a record-breaking 81 Emmy Award nominations across 14 hit Apple Original titles for this year's 77th Emmy Awa...
15/07/2025
Independent media outlets in Brazil and Colombia are invited to apply for a new programme aimed at strengthening the long-term resilience of journalism in the f...
15/07/2025
By Lucy Spicer
One of the most exciting things about the Sundance Film Festival...
15/07/2025
Spotify une fuerzas con DiDi, la app l der en servicios de movilidad, delivery y...
15/07/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
15/07/2025
L3Harris put its CORVUS-RAVEN counter-small UAS capability into the hands of soldiers at VANAHEIM, showcasing its ability to provide passive signal detect, enha...
15/07/2025
Netflix Viewing Up 13.5% vs. May, Represents 42% of Monthly Gain for Streaming
...
15/07/2025
SAN FRANCISCO and BENGALARU, India Sangeeta Chakraborty has been named chief revenue officer at Amagi, a cloud-based software-as-a-service (SaaS) technology pro...
15/07/2025
As part of its mandate, the Advanced Television Systems Committee the U.S. organization tasked with developing advanced broadcast TV standards promotes ATSC 3.0...
15/07/2025
QuickLink, the leading global provider of multi-camera video productions and remote contributions, announces the launch of two innovative control panels Studi...
15/07/2025
Chris Kontopanos has joined leading high-quality microphone solutions manufacturer, DPA Microphones, as the company's new Regional Sales Manager for the Mid...
15/07/2025
Magnifi by VideoVerse, a global leader in AI-powered video automation, has launched a major platform upgrade built to simplify live and archival video editing f...
15/07/2025
Telestream, a global leader in media workflow technologies, will preview its latest innovations at IBC2025, Stand 7.B21. This year's showcase highlights how...
15/07/2025
IBC2025 is set to transform the onsite experience for its global attendees with the launch of a pioneering new feature: full integration of Amsterdam's GVB ...
15/07/2025
Music, sport and technology collided in spectacular fashion as ASB GlassFloor powered the debut of Beats N Buckets, Germany's first Basketball meets Hip-Ho...
15/07/2025
The Collectv, the Emmy award-winning broadcast solutions and workflows consultancy - and winner of Broadcast Tech's Team of the Year is delighted to announc...
15/07/2025
SipRadius, the expert in secure, low latency media transport, will showcase how broadcasters and media companies can take control of fragmented IP workflows at ...
15/07/2025
Appear, the global leader in live production technology, today announced its strategic partnership with beIN ASIA PACIFIC, a leading multi-platform sports media...
15/07/2025
Company marks 15 years of innovation at the show
Broadpeak, a leader in streaming and monetization at scale, will return to IBC (Hall 1, Stand F83. RAI, Amster...
Unusual Antibodies in Cows Suggest New Ways to Make Therapies for People LA JOLLA, CA June 6, 2013 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 new study led by scientists from The Scripps Research Institute (TSRI) focusing on an extraordinary family of cow antibodies points to new ways to make human medicines.
