Nav: Home

Super-resolution microscopy reveals unprecedented detail of immune cells' surface

June 15, 2016

LA JOLLA--When the body is fighting an invading pathogen, white blood cells--including T cells--must respond. Now, Salk Institute researchers have imaged how vital receptors on the surface of T cells bundle together when activated.

This study, the first to visualize this process in lymph nodes, could help scientists better understand how to turn up or down the immune system's activity to treat autoimmune diseases, infections or even cancer. The results were published this week in the Proceedings of the National Academy of Sciences.

"We had seen these receptors cluster and reposition in cultured cells that were artificially stimulated in the lab, but we've never seen their natural arrangements in lymph nodes until now," says senior author Björn Lillemeier, an associate professor in Salk's Nomis Laboratories for Immunobiology and Microbial Pathogenesis, and the Waitt Advanced Biophotonics Center.

T cells are activated when receptors embedded in their outer membrane bind to other immune cells that have digested an antigen, such as a virus, bacteria or cancer cell. In turn, the activated T cells switch on cellular pathways that help the body both actively seek out and destroy the antigen and remember it for the future. In the past, by looking at T-cell receptors embedded in isolated cells under the microscope, researchers discovered that the receptors are arranged in clusters--called protein islands--that merge when the cells are activated.

Lillemeier wanted more detail on how the receptors are arranged in tissue and how that arrangement might change when the T cells are activated in living hosts. The team used a super-resolution microscope developed in the laboratory of co-senior author Hu Cang, assistant professor at Salk's Waitt Advanced Biophotonics Center and holder of the Frederick B. Rentschler Developmental Chair. This microscopy approach, called light-sheet direct stochastic optical reconstruction microscopy (dSTORM), let the researchers watch T cell receptors in the membranes of T cells in mouse lymph nodes at a resolution of approximately 50 nanometers.

The new imagery confirmed the previous observation that protein islands of T-cell receptors merge into larger "microclusters" when T cells are activated. But it also showed that, before cells are activated, the protein islands are already arranged in groups--dubbed "territories" by Lillemeier's team. "The pre-organization on the molecular level basically turns the T cell into a loaded gun," says Lillemeier.

The organization of surface receptors enables T cells to launch fast and effective immune response against antigens. Understanding how the molecular organization mediates the sensitivity of T cell responses could help researchers make the immune system more or less sensitive. In the case of autoimmune diseases, clinicians would like to turn down the immune system's activity, while turning up the activity could help fight infections or cancers.

The research could also have implications for understanding other receptors in the body, which have a wide range of functions both within and outside the immune system. "We think that most receptors on the surfaces of cells are organized like this," says Ying Hu, first author and postdoctoral researcher at the Salk Institute.
-end-
The work and the researchers involved were supported by grants from the NOMIS Foundation, the Waitt Foundation, the James B. Pendleton Charitable Trust, the National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the National Cancer Institute and the California Institute for Regenerative Medicine.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Salk Institute

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...