Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Stanford Researchers Discover Immune System’s Rules of Engagement

Published: Saturday, May 24, 2014
Last Updated: Saturday, May 24, 2014
Bookmark and Share
Study finds surprising similarities in the way immune system defenders bind to disease-causing invaders.

A study led by researchers at Stanford's School of Medicine reveals how T cells, the immune system's foot soldiers, respond to an enormous number of potential health threats.

X-ray studies at the Department of Energy's SLAC National Accelerator Laboratory, combined with Stanford biological studies and computational analysis, revealed remarkable similarities in the structure of binding sites, which allow a given T cell to recognize many different invaders that provoke an immune response.

The research demonstrates a faster, more reliable way to identify large numbers of antigens, the targets of the immune response, which could speed the discovery of disease treatments. It also may lead to a better understanding of what T cells recognize when fighting cancers and why they are triggered to attack healthy cells in autoimmune diseases such as diabetes and multiple sclerosis.

"Until now, it often has been a real mystery which antigens T cells are recognizing; there are whole classes of disease where we don't have this information," said Michael Birnbaum, a graduate student who led the research at the School of Medicine in the laboratory of K. Christopher Garcia, the study's senior author and a professor of molecular and cellular physiology and of structural biology.

"Now it's far more feasible to take a T cell that is important in a disease or autoimmune disorder and figure out what antigens it will respond to," Birnbaum said.

T cells are triggered into action by protein fragments, called peptides, displayed on a cell's surface. In the case of an infected cell, peptide antigens from a pathogen can trigger a T cell to kill the infected cell. The research provides a sort of rulebook that can be used with high success to track down antigens likely to activate a given T cell, easing a bottleneck that has constrained such studies.

Combination Approach

In the study, researchers exposed a handful of mouse and human T-cell receptors to hundreds of millions of peptides, and found hundreds of peptides that bound to each type. Then they compiled and compared the detailed sequence - the order of the chemical building blocks - of the peptides that bound to each T-cell receptor.

From that sample set, which represents just a tiny fraction of all peptides, a detailed computational analysis identified other likely binding matches. Researchers compared the 3-D structures of T cells and their unique receptors bound to different peptides at SLAC's Stanford Synchrotron Research Lightsource (SSRL).

"The X-ray work at SSRL was a key breakthrough in the study," Birnbaum said. "Very different peptides aligned almost perfectly with remarkably similar binding sites. It took us a while to figure out this structural similarity was a common feature, not an oddity - that a vast number of unique peptides could be recognized in the same way."

Researchers also checked the sequencing of the peptides that were known to bind with a given T cell and found striking similarities there, too.

"T-cell receptors are 'cross-reactive,' but in fairly limited ways. Like a multilingual person who can speak Spanish and French but can't understand Japanese, a receptor can engage with a broad set of peptides related to one another," Birnbaum said.

Impact on Biomedical Science

Finding out whether a given peptide activates a specific T-cell receptor has been a historically piecemeal process with a 20 to 30 percent success rate, involving burdensome hit-and-miss studies of biological samples. "This latest research provides a framework that can improve the success rate to as high as 90 percent," Birnbaum said.

"This is an important illustration of how SSRL's X-ray-imaging capabilities allow researchers to get detailed structural information on technically very challenging systems," said Britt Hedman, professor of photon science and science director at SSRL. "To understand the factors behind T-cell-receptor binding to peptides will have major impact on biomedical developments, including vaccine design and immunotherapy."

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 3,500+ scientific posters on ePosters
  • More than 5,100+ 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 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

X-ray Study May Aid in Designing Better Blood Pressure Drugs
New atomic-scale details could help create more effective medications with fewer side effects.
Thursday, April 30, 2015
SLAC X-ray Laser Brings Key Cell Structures into Focus
Experiment is Important Step Toward Atomic-Scale Imaging of Intact Biological Particles.
Monday, November 17, 2014
Scientific News
Step Toward Controlling Zika and Dengue Fever
UCLA scientists and colleagues identify structure of a molecule that kills mosquitoes carrying malaria and West Nile virus.
Uncovering Bacteria's Antibiotic Resistance
Scientists determine the structure and mechanisms of enzyme that deactivates an important antibiotic - rifampicin.
Diamond Light Source Scientists Publish 5000th Paper
Diamond’s milestone paper reveals findings on embryonic defects.
3D-Printing in Science: Conference Co-Staged with LABVOLUTION
LABVOLUTION 2017 will have an added highlight of a simultaneous conference, "3D-Printing in Science".
Cone Snail Venom Reveals Insulin Insights
Researchers found that a fast-acting insulin from the cone snail can bind and activate the human insulin receptor.
Designing Drugs with a Whole New Toolbox
Researchers develop methods to design small, targeted proteins with shapes not found in nature.
Protein Studies Discover Molecular Secrets
Two protein studies have mapped proteins that reveal the secrets to recycling carbon and healing cells.
Antibodies Block Norovirus’ Entrance into Cells
Scientists have uncovered a mechanism in the human body that targets and successfully blocks noroviruses.
Protein Findings Could Lead To New Class Of Antibiotics
Atomic-level images of a protein have revealed a characteristic that could form a basis of new antibiotic approach.
Worms Point Way Toward Viral Strategies
Rice University wins NIH grant to study how nematodes handle gastrointestinal viruses.

SELECTBIO Market Reports
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos