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Behind the picture: Don Mason and his T cell legacy

by Guest Author on 15 Mar 2021

Antibodies, antigens and T cells – we’re living through an extraordinary time where the language of immunology has become the everyday. And its testament to the decades-worth of effort by researchers like Don Mason, working together and building on previous research, that we have the knowledge and tools to understand, tackle and even prevent disease. Here, former colleague Neil Barclay, Emeritus EP Abraham Professor of Chemical Pathology, looks back on Don’s work, contributions and legacy.

Left to right: Don Mason, Alan Williams, Neil Barclay. Image credit: Sir William Dunn School of Pathology, University of Oxford

In 1985 there would have been nothing remarkable about this photo. But viewed through the lens of a pandemic, this intimate scene shows three Medical Research Council (MRC) scientists – Don Mason (left), Alan Williams (middle) and me (right) – doing something that has become almost unfamiliar this year.

Sitting next to each other without masks and social distancing, it captures a relaxed moment of us posing for an MRC newsletter. It also reflects the close working relationship between Don with his expertise in the cellular workings of the immune system and the more molecular approaches of Alan and myself.

From physics to medicine

Director of the MRC Cellular Immunology Unit at the Sir William Dunn School of Pathology at the University of Oxford, Don made major contributions to immunology in the UK as a researcher, working for MRC for 26 years – his whole immunology career.

He took an unconventional route into immunology, which came in useful later in his career, starting out by training and working as a physicist. But after going back to university to do medicine, he moved immediately into research in the then recently formed MRC Cellular Immunology Unit at the Sir William Dunn School of Immunology in Oxford.

Despite a lack of immunology research experience, Don’s colleagues immediately recognised his ability, and he became a tenured staff member in record time. He then ran a research group until he retired in 1999, firstly under the directorship of James Gowans, then Alan Williams and finally he became a director himself following the death of Alan Williams in 1992. His physics background was of help when his lab was one of the first to obtain a fluorescence cell sorter – a new way of separating out different types of cells for analysis – that would transform cell immunology in the late 1970s.

Pioneering immunology tools

Don’s immunology career tackled major questions in the field in a rigorous way and focused mainly on T cells, which contribute to the immune system’s response to infection. It was an exciting time to be working in immunology, with the discovery in 1975 that mouse monoclonal antibodies could be useful tools for studying the immune system in the lab due to their ability to recognise specific targets on cells.

Using one of the first monoclonal antibodies – that was later shown to recognise a molecule expressed on the surface of T cells in rats, known as CD4 – he showed that T cells could clearly be separated into different types with different roles.

Neil Barclay, Emeritus EP Abraham Professor of Chemical Pathology

Unveiling T cell types

Don is recognised in particular for his work on identifying subpopulations of T cells. These immune cells are key to recognising foreign ‘tags’, or antigens, displayed by immune cells which trigger the body’s immune response, eliminate infected cells and provide help in the production of antibodies.

One major discovery was that the CD4 group of T cells could be further split, using monoclonal antibodies made in the MRC Unit, into one type that mediates T cell responses and another that actively controls T cells which was later termed ‘regulatory T cells’. These so-called ‘Treg’ cells help prevent autoimmunity and Don’s discovery opened up ways to study how their behaviour can be changed to help control autoimmune diseases.

It was typical that Don was ahead of his time in developing new concepts rather than following the crowd. He argued that the specificity of the T cell receptors, which recognise foreign antigens, had to be broadly cross-reactive and not highly specific. This went against current dogma at the time which thought they would be highly specific like the antibody receptors on B cells. The cross-reactivity of T cell receptors is now widely accepted. It can be beneficial, giving the body immunity to a disease it has never been exposed to – something which has been observed in some cases of COVID-19. Or in the case of autoimmunity it can be detrimental, when the immune system turns on and destroys its own cells. After more than 20 years Don’s work, Mason, 1998, is still cited more than 30 times a year.

Training immunologists of the future

Don ran a small but effective group training students and post-docs over many years. Many have gone on to be successful immunologists in academia and industry and recognise the quality of his training, as well as his personal qualities of being a kind and understanding person.

In addition to his scientific excellence, Don had strong principles and concern for social issues.  He demonstrated against nuclear weapons in the 1970s, and until recently, worked first as a prison visitor and then corresponded with individual prisoners.

The picture also reflects the debate that was happening at the time in cellular immunology, which was dominated by phenomenology rather than scientific rigour. Much discussion went on as to how to address the immunology questions and develop suitable methods. Don was at the forefront of the revolution that changed immunology due to the application of techniques such as cell sorting, monoclonal antibodies and molecular immunology and will be remembered for his thoughtful and critical approaches.

Don Mason, MRC scientist, immunologist, colleague, and friend died on 13 January 2021 at the age of 86. He is survived by his wife, four children and three grandchildren.

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