When it comes to the immune system, we're all more alike than previously thought, study finds

September 01, 2010

SEATTLE - When it comes to the mechanics of the human immune system, we are all more alike than previously thought, according to a new study by scientists at Fred Hutchinson Cancer Research Center.

This finding has significant implications for developing new ways to detect, diagnose and treat cancer and diseases of the immune system, according to Harlan Robins, Ph.D., corresponding author of a paper detailing the research in the Sept. 1 issue of Science Translational Medicine.

Robins and colleagues developed a novel way to sequence millions of T-cell receptors, a critical component of the human adaptive immune system, simultaneously from a single sample. When comparing immune system profiles from different people, the researchers were surprised to find that we are all more alike than previously thought.

"We found that any two people may share tens of thousands of the exact same T-cell receptor. This is contrary to previous dogma that each person has a distinct set of T-cell receptors with little or no overlap between people," said Robins, Ph.D., a computational biologist and an assistant member of the Public Health Sciences Division at the Hutchinson Center.

The findings have diagnostic and therapeutic potential for autoimmune diseases and cancer.

"The strong similarity in the adaptive immune cells between different people suggests that the same disease will induce the same response in different people," Robins said. "The technology described in this paper can readily detect such a response, even if the magnitude of the immune reaction is small. Therefore, we potentially could use one or more of these shared T-cell responses as a diagnostic for a particular disease."

The part of the human immune system responsible for protection against novel pathogens, called the adaptive immune system, is composed of tens of millions of different subtypes of cells. Each cell subtype expresses a different receptor on its surface. These receptors are proteins, each of which has a unique shape so that together they can bind to a wide range of differently shaped pathogens. The set of receptors the researchers analyzed are called T-cell receptors, which develop in the thymus. Unlike the rest of the genes in the human genome, the genes that code for these T-cell receptors are not inherited; they develop separately in each person. The huge quantity and variety of T-cells in each person has prevented in-depth study - until now.

For the study, Robins and colleagues in the Hutchinson Center's Clinical Research Division sequenced more than five million T-cell receptor DNA strands from each of seven healthy donors. After comparing these sequences, they found two primary results.

First, the set of T-cell receptor sequences used by the human immune system is not a random cross section of all the possibilities, but a small subset with consistent properties that the scientists subsequently identified.

"Each person's adaptive immune system is far more alike than expected," Robins said.

Second, pair-wise comparisons of the T-cell receptors in the seven donors revealed that that tens of thousands of identical receptors are shared by each pair, even in people of different ethnicities.

This discovery has particular implications for autoimmune diseases and cancers, Robins said. For certain autoimmune diseases, such as Type 1 diabetes and multiple sclerosis, T-cells themselves are believed to play a causative role because they attack the body's cells. In Type 1 diabetes the adaptive immune system attacks the pancreatic islet cells, and for MS the immune system targets the cells that form the myelin sheaths around neurons in the brain and spinal cord. Most autoimmune diseases are diagnosed only after significant disease progression. However, by this time, irreparable cell damage has occurred.

"The results of our paper suggest that a specific set of T-cells that we can now detect are likely to play a causative role in the disease," Robins said. "Further, we can detect this targeted set much earlier than present diagnostics, perhaps saving vital cell function with the preventive administration of currently available therapeutics. And, because the T-cell clones are causative of the disease, they also double as therapeutic targets. In principle, a monoclonal antibody could be developed to target these T-cell clones and prevent the autoimmune attack."

The findings also present a potential new direction for cancer biomarkers to detect the disease early, while it is still curable. For many cancers, such as colon cancer, there is compelling evidence that a T-cell immune response is induced. The immune system operates through a process called clonal expansion. The set of T cells with specific receptors that bind to the infected cell make millions of copies of themselves to create an army to fight the full set of infected cells.

"Effectively, the immune system is an amplifier. So a very small tumor has the potential to induce a magnified immune response," Robins said. "We are readily able to detect such a response. The results of this paper suggest that multiple patients might have a similar response to the same type of tumor. Therefore, detection of these similar responses could be an early diagnostic for certain types of cancer."

The scientists developed sequencing technology called ImmunoSEQ and associated software called the ImmunoSEQ Analyzer to process and analyze the immense amount of data that the experiments produced. The Hutchinson Center has patents pending on the sequencing technologies, which have been licensed exclusively to Adaptive TCR Corporation, a local company offering the sequencing and analysis services commercially.
-end-
The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases funded the research.

Note for media only: Please contact Dean Forbes to obtain a copy of the paper or to schedule an interview with Robins.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.

Fred Hutchinson Cancer Research Center

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.