Empowering antibodies to better activate the immune system Scripps Research scientists discover that a higher ratio of antibodies to viral protein helps engage two specific types of immune cells.
April 21, 2025
LA JOLLA, CA Antibodies are best known for their ability to latch onto and neutralize bacteria, viruses and other pathogens. But these immune proteins can do more than that: They also activate other components of the immune system, which then go to work to clear an infection. A new study from Scripps Research explores the factors that influence how effectively antibodies engage specific immune cells.
Their results, described April 22, 2025 in Cell Reports, indicate that a higher ratio of antibodies to viral protein in this case, a part of HIV better engages two specific types of immune cells. While this discovery is most immediately applicable to experimental HIV vaccines, it has implications for the development of other drugs as well.
Many therapeutics and vaccines tap into antibodies' immune-stimulating function, says senior author Lars Hangartner, associate professor of immunology in the Department of Immunology and Microbiology at Scripps Research. Understanding the mechanisms that govern it will help us to develop new versions that are better at their jobs because they have the most assistance from this secondary function.
Hangartner's team employed an artificial intelligence (AI) tool for a key aspect of this research: designing altered versions of the HIV protein. This AI-based approach accelerated their work and could do the same for future projects.
Fine-tuned by the immune system to latch onto a particular site on a pathogen, Y-shaped antibodies bind to their targets with their arms. Meanwhile, the Fc region (or stem ) of the antibody attaches to other immune cells. These include phagocytes, which engulf infected cells, and natural killer cells, which perforate and poison them.
Previous research in Hangartner's lab and elsewhere has indicated that in many cases but not all this interaction bolsters antibodies effectiveness and improves protection against infection. But scientists know little about what determines how well, if at all, the Fc region stimulates immune cells.
Hangartner believed multiple factors could be at play, including binding location. Antibodies that target the same viral protein can bind to different spots on its surface, called epitopes. Likewise, the strength of the bond between the antibody and epitope can vary, as can the number of antibodies that bind near one another.
To answer these questions in the new study, Hangartner's team focused on a well-studied target, HIV's Env protein, which the virus uses to invade human cells. But Env's epitopes are highly complex and so not suitable for the experiments they had in mind, which included relocating the epitopes on the viral protein to study the importance of binding location. Instead, they used a smaller, simpler, more accommodating epitope derived from the influenza virus.
Even with the simpler flu epitope, conventional techniques for grafting it onto varying spots on Env would require considerable trial and error. What's more, the results would be limited by the protein's willingness to cooperate.
An AI tool called AlphaFold2 helped them work around these challenges. With AlphaFold2, they designed Env proteins with the flu epitope placed exactly where they wanted it. They then selected and refined those designs, before expressing the altered proteins.
They analyzed how relocating the epitope altered the behavior of two immune cells: natural killer cells and phagocytes. They also looked at how these two cell types responded when the antibodies formed weaker versus stronger bonds with the epitope. And finally, they evaluated how the cells reacted when one, two or three antibodies bound to a set of three Env proteins.
Of these three factors, only one appeared to matter: The ratio of antibodies to Env. Both immune cells became most destructive when three antibodies bound per set of Env proteins. While the phagocytes displayed a low level of activity with a single antibody, natural killer cells had almost no response unless at least two were present.
This research suggests that HIV vaccines could also enhance the response from these other immune cells, in addition to eliciting the immune system to produce antibodies against the virus. Experimental vaccines that produce antibodies that can bind at high ratios appear most likely to take advantage of this secondary effect.
Antibody ratio appears to influence these interactions in other infectious diseases as well, according to Hangartner.
I think this rule is probably true for many other pathogens, Hangartner says, cautioning that only experiments will show whether such changes translate into better protection from disease. It's likely but not a given.
It's not clear yet if binding ratio's influence extends beyond infections to therapeutic antibodies, like those that target cancer cells or errant immune cells that promote inflammation. But, in general, Hangartner says, a better understanding of how these interactions activate other parts of the immune system could speed the development of these treatments.
In addition to Hangartner, authors of the study, Molecular parameters governing Fc R signaling and effector functions in the context of HIV envelope, include Michael Bick, Eduard Puig, David Beauparlant, Rebecca Nedellec, Iszac Burton, Keihvan Ardaghi, Thea R. Zalunardo, Raiza Bastidas, Xuduo Li, Javier Guenaga, Wen-Hsin Lee, Richard Wyatt, Wenwen Zhu of the University of Southamptom, Max Crispin, Gabriel Ozorowski, Andrew Ward, and Dennis Burton of Scripps Research.
This study was supported by funding from the National Institutes of Health (UM1Al44462 and R01 Al136621-0
Most recent headlines
09/11/2025
Dalet today announced a transformative leap forward for media operations: Agentic Artificial Intelligence (AI) that unifies the Dalet ecosystem under one natura...
16/10/2025
Parks Associates has released new data showing that nearly half (45%) of U.S. internet homes watch free ad-supported streaming TV (FAST) services and 89% of U.S...
16/10/2025
TROY, Mich. -New data from J.D. Power's 2025 U.S. Residential Internet Service Provider Study shows that residential wireless internet providers are growing...
15/10/2025
Across the world, early-career reporters are interrogating systems that shape daily life, from mortuaries and classrooms to the corridors of legal education and...
15/10/2025
St. Louis Blues Pay Tribute to Ozzy Osbourne in New Pregame Open VideoThe NHL franchise worked with production firms 2WEI and 4th Floor CreativeBy Mark J Burns,...
15/10/2025
Cobalt Digital, G3DVu, Proxima Vision, and Telos Alliance Renew Premier Sponsors...
15/10/2025
By Paige Bethmann
Before my grandmother passed away in 2019, I went to visit her in the hospital where she'd been for a few weeks. When I arrived, the nurs...
15/10/2025
Two years ago, Spotify set out to grow the entire publishing industry by making ...
15/10/2025
People turn to DJ for a listening experience that feels personal, dynamic, and j...
15/10/2025
Las personas recurren a DJ para vivir una experiencia de escucha personal, din m...
15/10/2025
Rock legend Bruce Springsteen and luminary actor Jeremy Allen White came togethe...
15/10/2025
At Spotify, we're all about supporting rising talent and helping them connec...
15/10/2025
New SBS Documentary Series THE CANCER KILLERS Premieres 4 November on SBS & SBS ...
15/10/2025
SBS celebrates the Festivals of Lights with bold, illuminating stories across th...
15/10/2025
One of humanity's most profound questions continues: Is there any place in our galaxy suitable for life beyond Earth? NASA intends to find out, with the hel...
15/10/2025
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({ content_source:......
15/10/2025
Scality, a global leader in cyber-resilient storage software for the AI era, today announced the advancement of its comprehensive AI ecosystem certification pro...
15/10/2025
The Hollywood Professional Association (HPA) today unveiled key highlights of the 2026 HPA Tech Retreat, scheduled for Feb. 15 19 at the Westin Rancho Mirage Go...
15/10/2025
At NAB Show New York 2025 (Stand 244), Interra Systems will showcase the future of media QC, monitoring, and captioning, highlighting its award-winning, AI- and...
15/10/2025
Grass Valley today announced that RMC BFM, part of the CMA-CGM Group and France's third-largest private media group, has chosen Grass Valley's productio...
15/10/2025
Appear, the global leader in live production technology, will demonstrate how its powerful hardware and software innovations are shaping the future of hybrid, s...
15/10/2025
Rakim to Join Berklee's Hip-Hop Hall of Fame at Signature Series Concert The rap icon becomes the latest inductee, following luminaries such as Roxanne Sh...
15/10/2025
Berklee Brings Live Music to the Head of the Charles Student artists will perform on multiple riverfront stages during the 60th anniversary of the world's...
15/10/2025
CobbTV, the government access television channel for Cobb County, Ga. recently acquired an automated playout system from Pebble, a global provider of automation...
15/10/2025
OSLO, Norway Appear, the global leader in live production technology, will demonstrate how its powerful hardware and software innovations are shaping the future...
15/10/2025
NEW YORK The NBA is making major changes to the NBA App and NBA TV as it takes control of them from TNT Sports, which has long managed the league's digital ...
15/10/2025
SAN MATEO, Calif. In what promises to be a major expansion of interactive features and personalized content on the DirecTV platform, the operator and Glance hav...
15/10/2025
SAN JOSE, Calif. Roku has launched changes to its user interface (UI) that the streaming platform says will better showcase original programming on the platform...
15/10/2025
LOS ANGELES Software-defined data storage and data services provider OpenDrives has elevated Alex Dunfey to chief technology officer, responsible for driving th...
15/10/2025
Abu Dhabi, UAE October 15, 2025: Space42 (ADX: SPACE42), the UAE-based AI-powe...
15/10/2025
Sheldon Nichols and Will Trickett to find and prepare more classic cars for budget conscious would-be owners from Wiser Films
UKTV have recommissioned the clas...
15/10/2025
Wednesday 15 October 2025
Nick Cave
JPEG (275 KB)
Explore the creative univer...
15/10/2025
Wednesday 15 October 2025
From breaking up with your partner to quitting your job - new polling shows some messages are just too scary to send
Over a fifth (...
15/10/2025
Rohde & Schwarz unveils compact MXO 3 oscilloscopes with 4 and 8 channels: Advan...
15/10/2025
Back to All News
Revenge Series The Resurrected' Captivates Audiences Across Asia
Entertainment
15 October 2025
GlobalTaiwan
Link copied to clipboard
...
15/10/2025
Back to All News
Bringing the Best in VFX and Virtual Production Together as Eyeline
Jeffrey Shapiro
CEO, Eyeline
Business
15 October 2025
GlobalCanadaInd...
15/10/2025
Deployed by Astound Business Solutions, Harmonic's Primary Distribution Solution Ensures Outstanding Video Quality and Seamless Ad Insertion at the Edge
SA...
15/10/2025
Collaboration extends a trusted relationship as RMC BFM invests in scalable, fut...
15/10/2025
Series coming in 2026 stars Tom Vaughan-Lawlor, Justine Mitchell and Jason O'Mara released today
RT today released first look images of new comedy-drama ...
14/10/2025
SVG Europe Summit 2025: All Sessions Now Available to Watch on SVG PLAYNetworking event that preceded IBC2025 shone a light on elite live sports innovation acro...
14/10/2025
SVG Sit-Down: Author Rich Podolsky on Writing Madden & Summerall: How They Revo...
14/10/2025
SVG All-Stars: Michael Reiners, Coordinating Producer, FloRacingThe Illinois State grad steers a vast schedule of motorsports events at tracks across the countr...
14/10/2025
Content protection: Getting the right management for your DRM By Neal Romanek
Friday, October 10, 2025 - 10:11
Print This Story
Eluvio power the EPCR'...
14/10/2025
As League Takes Over Ops, NBA TV and NBA App Add 60 Games, Weekday Studio Show, ...
14/10/2025
Time and effort: World's largest student-led broadcast prepares to go On Air...
14/10/2025
(L-R) Guest, Kimberly Robinson Jones, Geeta Gandbhir, Pamela Dias, and Takema Ro...
14/10/2025
Lossless ist jetzt mit Spotify Premium verf gbar.
Verlustfreies Audio war eine...
14/10/2025
La qualit Lossless est disponible sur Spotify Premium.
Le format sans perte de...
14/10/2025
For the seventh edition of Spotify and FC Barcelona's artist jersey series, ...
Empowering antibodies to better activate the immune system Scripps Research scientists discover that a higher ratio of antibodies to viral protein helps engage two specific types of immune cells. 
