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Novel Mechanism Discovered In First Line of Immune Defence

A*STAR scientists’ discovery opens doors to developing new therapies to eradicate tumour cells and combat infections

1. Scientists from A*STAR’s Singapore Immunology Network (SIgN) have discovered a new defense mechanism that the immune system utilises to combat infections. The team’s discovery of how a novel protein unexpectedly activates an immune response shows how this mechanism can also be used to get rid of tumour cells. This research was done in collaboration with University Hospital Basel, Switzerland, published in July 2013 in Nature Immunology.

2. The immune system combats microbes using several strategies, of which early activation of defence is one of the most important. The mechanisms used by the immune system to counterattack microbes often rely on the immediate recognition of microbes, or of cells that have been affected by the infection of microbes.

3. The team at SIgN led by Prof Gennaro De Libero has identified a novel mechanism of how the immune system readily detects invading microbes and effectively initiates early immune responses, by activating a special class of cells called gamma delta lymphocytes. Gamma delta lymphocytes were discovered more than 30 years ago and had been identified as cells that are capable of early protection as they play a decisive role in the first line of immune defence. However, many studies into discovering the mechanisms of how these cells are activated when microbes attack have been unfruitful.

4. The team’s discovery of a protein called Butyrophilin 3A1 shows how it binds to microbial antigens and hence activates human gamma delta cells. These cells are then able to coordinate an immune response to clear the infection caused by invading microbes.

5. This protein has also been found to bind antigens that are produced in large amounts in tumour cells, which then activates gamma delta cells against these tumour cells. The discovery of this mechanism thus represents a novel target that will help to eradicate tumours and combat infections.

6. Prof De Libero said, “The identification of the molecular mechanisms of how human gamma delta cells get activated opens doors to novel opportunities for immunotherapy of infections and tumours.”

7. Prof Philippe Kourilsky, Chairman of SIgN said, “This study is a breakthrough in immunology and also an excellent example of basic science as an important premise to medicine.”

8. Prof Laurent Rénia, Acting Executive Director of SIgN said, “We are delighted that this excellent science has paved the way for many others in immunology and other fields. I believe that these findings present great promise in developing new treatments for cancer therapy and infectious diseases.”

Notes for Editor:

The research findings described in this media release can be found in the 21 July 2013 online issue of Nature Immunology under the title, “Butyrophilin 3A1 binds phosphorylated antigens and stimulates human gamma delta T cells” by Stefano Vavassori1,#, Anil Kumar2,#, Gan Siok Wan2, Gundimeda S Ramanjaneyulu1, Marco Cavallari1, Sary El Daker2, Travis Beddoe3, Alex Theodossis3, Neal K Williams3, Emma Gostick4, David A Price4, Dinish U Soudamini5, Kong Kien Voon5, Malini Olivo5, Jamie Rossjohn3,4, Lucia Mori1,2 & Gennaro De Libero1,2

1 Experimental Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland

2 Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore

3 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia

4 Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK

5 Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Biopolis, Singapore

# These authors contributed equally to this work.
Correspondence should be addressed to G.D.L. (


For media queries and clarifications, please contact:

Vithya Selvam (Ms)

Corporate Communications

Agency for Science, Technology and Research

Tel: (+65) 6826 6291



About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.

A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners.

For more information about A*STAR, please visit

About the Singapore Immunology Network (SIgN)

The Singapore Immunology Network (SIgN), officially inaugurated on 15 January 2008, is a research consortium under the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research Council. The mandate of SIgN is to advance human immunology research and participate in international efforts to combat major health problems. Since its launch, SIgN has grown rapidly and currently includes 250 scientists from 26 different countries around the world working under 28 renowned principal investigators. At SIgN, researchers investigate immunity during infection and various inflammatory conditions including cancer and are supported by cutting edge technological research platforms and core services.

Through this, SIgN aims to build a strong platform in basic human immunology research for better translation of research findings into clinical applications. SIgN also sets out to establish productive links with local and international institutions, and encourage the exchange of ideas and expertise between academic, industrial and clinical partners and thus contribute to a vibrant research environment in Singapore.

For more information about SIgN, please visit

Vithya Selvam | EurekAlert!
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