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T cells can mount attacks against many SARS-CoV-2 targets–even on new virus variant

New LJI research gives detailed look at vulnerable sites on the novel coronavirus–beyond the receptor binding domainCredit: NIAID LA JOLLA–A



New LJI research gives detailed look at vulnerable sites on the novel coronavirus–beyond the receptor binding domain

LA JOLLA–A new study led by scientists at La Jolla Institute for Immunology (LJI) suggests that T cells try to fight SARS-CoV-2 by targeting a broad range of sites on the virus–beyond the key sites on the virus’s spike protein. By attacking the virus from many angles, the body has the tools to potentially recognize different SARS-CoV-2 variants.

The new research, published January 27, 2021 in Cell Report Medicine, is the most detailed analysis so far of which proteins on SARS-CoV-2 stimulate the strongest responses from the immune system’s “helper” CD4+ T cells and “killer” CD8+ T cells.

“We are now armed with the knowledge of which parts of the virus are recognized by the immune system,” says LJI Professor Alessandro Sette, Dr. Biol. Sci., who co-led the new study with LJI Instructor Alba Grifoni, Ph.D.

Sette and Grifoni have led research into immune responses to the virus since the beginning of the pandemic. Their previous studies, co-led by members of the LJI Coronavirus Task Force, shows that people can have a wide range of responses to the virus–some people have strong immune responses and do well. Others have disjointed immune responses and are more likely to end up in the hospital.

As COVID-19 vaccines reach more people, LJI scientists are keeping an eye on how different people build immunity to SARS-CoV-2. They are also studying how T cells could combat different variants of SARS-CoV-2. This work takes advantage of the lab’s expertise in predicting and studying T cell responses to viruses such as dengue and Zika.

“This is even more important with COVID-19 because it is a global pandemic, so we need to account for immune responses in different populations,” says Grifoni.

The immune system is very flexible. By re-scrambling genetic material, it can make T cells that respond to a huge range of targets, or epitopes, on a pathogen. Some T cell responses will be stronger against some epitopes than others. Researchers call the targets that prompt a strong immune cells response “immunodominant.”

For the new study, the researchers examined T cells from 100 people who had recovered from SARS-CoV-2 infection. They then took a close look at the genetic sequence of the virus to separate the potential epitopes from the epitopes that these T cells would actually recognize.

Their analysis revealed that not all parts of the virus induce the same strong immune response in everyone. In fact, T cells can recognize dozens of epitopes on SARS-CoV-2, and these immunodominant sites also change from person to person. On average, each study participant had the ability to recognize about 17 CD8+ T cells epitopes and 19 CD4+ T cell epitopes.

This broad immune system response serves a few purposes. The new study shows that while the immune system often mounts a strong response against a particular site on the virus’s “spike” protein called the receptor binding domain, this region is actually not as good at inducing a strong response from CD4+ helper T cells.

Without a strong CD4+ T cell response, however, people may be slow to mount the kind of neutralizing immune response that quickly wipes out the virus. Luckily, the broad immune response comes in handy, and most people have immune cells that can recognize sites other than the receptor binding domain.

Among the many epitopes they uncovered, the researchers identified several additional epitopes on the SARS-CoV-2 spike protein. Grifoni says this is good news. By targeting many vulnerable sites on the spike protein, the immune system would still be able to fight infection, even if some sites on the virus change due to mutations.

“The immune response is broad enough to compensate for that,” Grifoni says.

Since the announcement of the fast-spreading UK variant of SARS-CoV-2 (called SARS-CoV-2 VUI 202012/01), the researchers have compared the mutated sites on that virus to the epitopes they found. Sette notes that the mutations described in the UK variant for the spike protein affect only 8% of the epitopes recognized by CD4+ T cells in this study, while 92% of the responses is conserved.

Sette emphasized that the new study is the results of months of long hours and international collaboration between labs at LJI; the University of California, San Diego; and researcher’s at Australia’s Murdoch University. “This was a tremendous amount of work, and we were able to do it really fast because of our collaborations,” he says.


The study, “Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases,” was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (AI42742 ,75N9301900065 and 75N93019C00001), the National Institutes of Health (U01 CA260541-01, AI135078, and AI036214); UCSD T32s (AI007036 and AI007384), the Jonathan and Mary Tu Foundation and the University of Genoa, Italy.

Additional study authors include first author Alison Tarke, John Sidney, Conner Kidd, Jennifer M. Dan, Sydney I. Ramirez, Esther Dawen Yu, Jose Mateus, Ricardo da Silva Antunes, Erin Moore, Paul Rubiro, Nils Methot, Elizabeth Phillips, Simon Mallal, April Frazier, Stephen A. Rawlings, Jason A. Greenbaum, Bjoern Peters, Davey M. Smith, Shane Crotty and Daniela Weiskopf.


About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.



Army technique enhances robot battlefield operations

Credit: (Photo illustration / U.S. Army) ADELPHI, Md. — Army researchers developed a technique that allows robots to remain resilient



Credit: (Photo illustration / U.S. Army)

ADELPHI, Md. — Army researchers developed a technique that allows robots to remain resilient when faced with intermittent communication losses on the battlefield.

The technique, called α-shape, provides an efficient method for resolving goal conflicts between multiple robots that may want to visit the same area during missions including unmanned search and rescue, robotic reconnaissance, perimeter surveillance and robotic detection of physical phenomena, such as radiation and underwater concentration of lifeforms.

Researchers from the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory and the University of Nebraska, Omaha Computer Science Department collaborated, which led to a paper featured in ScienceDirect’s journal Robotics and Autonomous Systems.

“Robots working in teams need a method to ensure that they do not duplicate effort,” said Army researcher Dr. Bradley Woosley. “When all robots can communicate, there are many techniques that can be used; however, in environments where the robots cannot communicate widely due to needing to stay covert, clutter leading to radios not working for long distance communications, or to preserve battery or bandwidth for more important messages, the robots will need a method to coordinate with as few communications as possible.”

This coordination is accomplished through sharing their next task with the team, and select team members will remember this information, allowing other robots to ask if any other robot will perform that task without needing to communicate directly with the robot that selected the task, Woosley said.

The robot that remembers a task is based on the topology of their wireless communications network and the geometric layout of the robots, he said. Each robot is assigned a bounding shape representing the area of the environment that they are caching goal locations for, which enables a quick search in the communications network to find the robot that would know if there were any goals requested in that area.

“This research enables coordination between robots when each robot is empowered to make decisions about its next tasks without requiring it to check in with the rest of the team first,” Woosley said. “Allowing the robots to make progress towards what the robots feel is the most important next step while handling any conflicts between two robots as they are discovered when robots move in and out of communications range with each other.”

The technique uses a geometric approximation called α-shape to group together regions of the environment that a robot can communicate with other robots using multi-hop communications over a communications network. This technique is integrated with an intelligent search algorithm over the robots’ communication tree to find conflicts and store them even if the robot that selects the goal disconnects from the communication tree before reaching the goal.

The team reported experimental results on simulated robots within multiple environments and physical Clearpath Jackal Robots.

“To our knowledge, this work is one of the first attempts to integrate geometry-based prediction of potential conflict regions to improve multi-robot information collection under communication constraints, while gracefully handling intermittent connectivity loss between robots,” Woosley said.

According to Woosley, other available approaches can only get input from the robots that are inside the same communications network, which is less efficient when robots can move in and out of communications range with the team.

In contrast, he said, this research provides a mechanism for the robot to quickly find potential conflicts between its goal and the goal another robot selected, but is not in the communications network anymore.

What specifically makes this research unique includes:

    -Providing an efficient method (fast and with few messages) for resolving goal conflicts between multiple robots that is robust to intermittent communications loss and robots joining or leaving local sets of robots that are in communications with each other

    -Performing as good as querying every robot in the communications range while saving radio bandwidth for more important communications

    -Performing better than each robot operating fully on its own without communications

Woosley said that he is optimistic this research will pave the way for other communications limited cooperation methods that will be helpful when robots are deployed in a mission that requires covert communications.

He and the research team, including DEVCOM ARL researchers Dr. John Rogers and Jeffrey Twigg and Naval Research Laboratory research scientist Dr. Prithviraj Dasgupta, will continue to work on collaboration between robotic team members through limited communications, especially in directions of predicting the other robot’s actions in order to avoid conflicting tasks to begin with.


Researchers from the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory and the University of Nebraska, Omaha Computer Science Department collaborated, which led to a paper featured in ScienceDirect’s journal Robotics and Autonomous Systems.


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Dean Sam H. Noh named 2020 ACM fellow

Credit: UNIST Sam H. Noh, Professor of Electrical and Computer Engineering and Dean of the Graduate School of Artificial Intelligence



Sam H. Noh, Professor of Electrical and Computer Engineering and Dean of the Graduate School of Artificial Intelligence at UNIST, has been elected as a 2020 fellow of the Association for Computing Machinery (ACM), the world’s largest scientific and educational society for computing professionals.

The ACM Fellows program recognizes the top 1% of ACM members for their outstanding accomplishments in computing and information technology and/or outstanding service to ACM and the larger computing community. Fellows are nominated by their peers, with nominations reviewed by a distinguished selection committee.

Among the 95 professionals named to the 2020 cohort, Professor Noh was the only scientist, affiliated with a Korean university. To date, only four scientists that are affiliated with Korean universities, including Professor Noh, have been elected as ACM fellows.

The 95 ACM Fellows selected this year from the world’s leading universities, corporations, and research labs have achieved advances in areas including artificial intelligence, cloud computing, computer graphics, computational biology, data science, human-computer interaction, software engineering, theoretical computer science, and virtual reality, the ACM said.

As noted by ACM President Gabriele Kotsis, “The 2020 ACM Fellows have demonstrated excellence across many disciplines of computing. These men and women have made pivotal contributions to technologies that are transforming whole industries, as well as our personal lives.” She added, “We fully expect that these new ACM Fellows will continue in the vanguard in their respective fields.”

Professor Sam H. Noh is a prominent scientist in system software and data storage technology. Besides being appointed as Editor-in-Chief of the ACM Transaction of Storage (ToS) in 2016, he has been contributing greatly to the academic vitality of the computing field. In 2017, he was honored as a Distinguished Member of the ACM in recognition of his contributions to advancing the field of computing. Professor Noh has also gained international attention in February 2020 when he served as one of two co-chairs for the USENIX ’18th USENIX Conference on File and Storage Technologies’ (FAST ’20).

Professor Noh received the B.S. degree in computer engineering from Seoul National University and the Ph.D. degree in computer science from University of Maryland. He joined the Department of Electrical and Computer Engineering at UNIST in 2015. Prior to joining UNIST, Professor Noh worked at George Washington University and Hongik University for the last 22 years. He currently serves as the Dean of Graduate School of Artificial Intelligence at UNIST. His research interests include operating system issues pertaining to embedded/computer systems with a focus on the use of new memory technologies, such as flash memory and persistent memory.



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Horticulture Research welcomes Dr. Steven van Nocker as the Executive Editor

Credit: Michigan State University Horticulture Research is pleased to announce the appointment of Dr. Steven van Nocker as the journal’s



Horticulture Research is pleased to announce the appointment of Dr. Steven van Nocker as the journal’s Executive Editor from 2021.

Dr. Steven van Nocker, a Professor in the Department of Horticulture at Michigan State University, USA, received a B.S. in Biology and Genetics from Cornell University, USA and a Ph.D. in Cellular and Molecular Biology from the University of Wisconsin, USA. His research focuses on the developmental genetics of traits important for horticultural crop production including flowering, as well as the regulation of gene expression during development. This academic background and research experience in the field of horticulture and molecular biology is well suited for the current and future editorial needs of Horticulture Research. Dr. van Nocker was one of the inaugural Associate Editors and has played a significant role in building Horticulture Research as a leading international journal in horticulture, plant science, and genetics. To date, he has handled over 60 manuscripts as Associate Editor, and has participated in the review of many additional manuscripts.

“Steve has graciously accepted my invitation and I greatly appreciate his willingness to step into this new role and take the challenge.” said Prof. Max Cheng, Editor-in-Chief of Horticulture Research. “Research focusing on plants of horticultural importance offers almost limitless opportunities to tackle longstanding, interesting and fundamental questions in plant biology” commented Dr. van Nocker. “New practical knowledge and discoveries will find immediate application to problems related to food, environment, and human health and nutrition. Horticulture Research has a critical role to highlight the most important of these, and I’m very excited for this opportunity to be involved.”



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