'Mix and match' assembly instructions guide immune cell attacks

September 5, 2017, Walter and Eliza Hall Institute of Medical Research
'Mix and match' assembly instructions guide immune cell attacks
Associate Professor Matthew Call (left) and Dr Melissa Call discovered a unique way that immune cells respond to, and kill, diseased and cancerous cells. Credit: Walter and Eliza Hall Institute of Medical Research

Institute researchers have discovered how immune cells use a unique set of assembly instructions to 'mix and match' how they respond to, and kill, tumour and diseased cells.

Cell surface receptor complexes are like Lego pieces, constructed using different molecular combinations to guide how the immune cell acts when it makes contact with a cancerous cell, an infection, or other external signals. The new research identifies the features that allow these pieces to assemble in specific combinations.

Understanding how these complexes assemble 'naturally' could pave the way for future improvements in immunotherapy, such as engineering -specific immune killers.

Associate Professor Matthew Call and Dr Melissa Call from the Walter and Eliza Hall Institute led the research with colleagues in Spain and the US, published in the journal Proceedings of the National Academy of Sciences.

Associate Professor Matthew Call said the team discovered an entirely new set of assembly instructions used by molecular sensors embedded in the thin fatty cell membrane to build receptor complexes in response to different stimuli.

"Effectively, these membrane-bound sensors determine 'who' the immune cell talks to. This is really important in the promising field of cancer immunotherapy, because it could help us better engineer cells to specifically talk to – and destroy – cancer cells," Associate Professor Matthew Call said.

Cell surface receptor complexes consist of an external receptor that binds to signalling molecules, an internal molecule that instructs the cell how to respond, and a cell membrane-embedded portion that anchors and links the other two segments.

In the past, these cell membrane-embedded sections of the receptor were largely ignored, partly because they are so difficult to work with, Associate Professor Matthew Call said.

"However more and more we are discovering what a critical role they play in how signals are received and acted upon by the cell. In fact, the sensors found in the fatty cell membrane actually control how the cell responds to external signals by pulling different external and internal sections together like building blocks to drive the correct response," he said.

The researchers began by studying the on natural killer (NK) cells, but found that the same assembly instructions were used in a host of immune cells that "run around and eat and blow up" cancerous and other , Dr Melissa Call said.

"One subset of these receptors, called Fc receptors, were the focus of this research. We were particularly looking at the subset of Fc receptors found on natural killer (NK) cells – immune cells that poison tumour and virus-infected that have been 'marked' by antibodies," Dr Melissa Call said.

She said the study showed that different subsets of Fc receptors used completely different assembly instructions compared to other, similar receptors.

"Over the past decade or so, this has become really important therapeutically because of a new field of cancer immunotherapy called chimeric antigenic receptor therapy, or CART," Dr Melissa Call said.

"The idea of CART is that you create specially engineered receptors in that are highly specific for an individual cancer. Understanding in depth how these receptors are assembled naturally is vital for us to understand how best to design them ourselves for cancer therapy, to look at improved ways of stimulating the immune response to cancer."

Dr Melissa Call said the laboratory's long-term goal was to decipher and control how immune receptors work, to find new ways of manipulating the immune response for therapeutic treatments.

"Controlling how the are assembled could allow us to boost the immune response in the case of infections or immune deficiencies, dampen it down in the case of autoimmune disease, or redirect the to better target cancers," she said.

Explore further: Researchers makes 'natural born killer' cell discovery

More information: Alfonso Blázquez-Moreno et al. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1706483114

Related Stories

Researchers makes 'natural born killer' cell discovery

August 31, 2017
An unexpected role for a white blood cell called the Natural Killer (NK) cell - a critical cell for ridding the body of infection and cancer, has been discovered by researchers at New Zealand's University of Otago.

Researchers create a 'Rosetta Stone' to decode immune recognition

June 21, 2017
Scientists from St. Jude Children's Research Hospital and Fred Hutchinson Cancer Research Center have developed an algorithm that functions like a Rosetta Stone to help decipher how the immune system recognizes and binds ...

Engineering the immune system to kill cancer cells

June 15, 2016
In late 2015, former President Jimmy Carter announced that he was free of the metastatic melanoma that had spread to his liver and brain. In addition to surgery and radiation, Carter was treated with an immunotherapy drug, ...

Immune receptors amplify 'invader' signals by turning into mini-machines

November 21, 2016
When a receptor on the surface of a T cell—a sentry of the human immune system—senses a single particle from a harmful intruder, it immediately kicks the cell into action, launching a larger immune response. But exactly ...

Artificial receptors kill cells infected with the virus that causes AIDS, study finds

July 15, 2016
A type of immunotherapy that has shown promising results against cancer could also be used against HIV, the virus that causes AIDS.

New model of T cell activation

May 27, 2016
T cell receptors are an important part of the human immune system. They are able to switch their conformation from an inactive to an active state spontaneously without any antigens present. Cholesterol binds and stabilizes ...

Recommended for you

Thymic tuft cells play key role in preventing autoimmunity, mouse experiments show

July 18, 2018
UC San Francisco researchers were recently surprised to discover fully formed gut and skin cells in the thymus, a lemon-sized organ that sits in front of the heart and is responsible for training the T cells of the immune ...

Autism risk determined by health of mom's gut, research reveals

July 18, 2018
The risk of developing autism-spectrum disorders is determined by the mother's microbiome—the collection of microorganisms that naturally live inside us—during pregnancy, new research from the University of Virginia School ...

New findings suggest allergic responses may protect against skin cancer

July 17, 2018
The components of the immune system that trigger allergic reactions may also help protect the skin against cancer, suggest new findings.

The immune system: T cells are built for speed

July 17, 2018
Without T cells, we could not survive. They are a key component of the immune system and have highly sensitive receptors on their surface that can detect pathogens. The exact way that these receptors are distributed over ...

Broadly acting antibodies found in plasma of Ebola survivors

July 17, 2018
Recent Ebola virus disease (EVD) outbreaks, including the 2013-2016 epidemic that ravaged West Africa and the 2018 outbreak in the Democratic Republic of the Congo, highlight the need for licensed treatments for this often-deadly ...

How protein fragments could help to tackle the cause of hay fever

July 16, 2018
Imperial researchers are looking to protein fragments to help people build up resistance to grass pollen.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.