Discovering new regulators of the immune system

September 14, 2003

London, U.K. and South San Francisco, CA, 15th September 2003. In an attempt to find new regulators of the immune system, a team of researchers at Rigel Pharmaceuticals, Inc. have created a successful method for discovering molecules that are involved in signalling pathways. As published this week in the Journal of Biology, the team conducted a functional genome-wide screen and discovered novel modulators of T-cell receptor signalling that could aid in the development of drugs that target the immune response.

T cells are an integral part of the immune response. Helper T cells encourage antibody-producing B cells to replicate and secrete antibodies, and play a role in the inflammatory response. Cytotoxic T cells identify and kill cells that have been infected with viruses. As all these functions are initiated by T-cell receptors, each response must be determined by the particular set of downstream signalling components that are activated. Until now, identifying novel components of these pathways has been slow. As the article notes, the researchers believe that this study demonstrates, "a successful approach for discovering and validating, in a functionally relevant context, important immune regulators on a genome-wide scale."

The research team, led by Dr. Charlene Liao, as part of a collaboration with Novartis, used retroviruses to carry into cells lymphoid genes that regulate T-cell receptor signalling when expressed. Normally, a cell surface marker called CD69 is up regulated when T-cell receptors are activated. However, the researchers selected cells that, when given a new gene to express, failed to up regulate this protein. They then checked that this repression was caused by the introduced gene and was not a side effect of the procedure. After three rounds of selection, 33 individual genes were cloned. Some of these were already known to play a role in the immune response, some already had unrelated functions assigned to them, and others were completely novel.

The Rigel team carried out additional experiments on three of the genes that were identified in the screen to verify their functional relevance. These experiments confirmed that the genes EDG1, PAK2, and the previously unidentified TRAC-1 were normally expressed in the lymphoid system and that truncated versions of the proteins they produce could repress T-cell receptor signalling in T-cells.

The authors write: "This approach provides a tool for functional cloning of regulators in numerous signal transduction pathways. [...] Importantly, the outlined strategy, which requires no prior sequence information of the players involved, does not bias the search to previously known signalling molecules, molecules flagged by DNA-array technologies or signalling molecules discovered in other contexts."
-end-
Once published, this article will be freely available online, in keeping with BioMed Central's policy of open access to research articles:

Systematic Identification of Regulator Proteins Critical for T Cell activation
Peter Chu, Jorge Pardo, Haoran Zhao, Connie C Li, Erlina Pali, Mary M Shen, Kunbin Qu, Simon X Yu, Betty C B Huang, Peiwen Yu, Esteban S Masuda, Frank Kolbinger, Gregorio Aversa, Jan de Vries, Donald G Payan and X Charlene Liao.
Journal of Biology 2:21
http://jbiol.com/content/2/3/21
Published 15th September 2003

Please publish the URL in any news report so that your readers will be able to read the original paper.

Contact Dr. Donald G. Payan Rigel's CSO and Executive Vice President (dgpayan@rigel.com) for further information about this research.

Alternatively contact Gemma Bradley by email at press@biomedcentral.com or by phone on 44-207-323-0323.

Journal of Biology (http://jbiol.com) is published by BioMed Central (http://www.biomedcentral.com), an independent online publishing house committed to providing immediate free access to peer-reviewed biological and medical research. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science. In addition to open-access original research, BioMed Central also publishes reviews and other subscription-based content.

About Rigel Pharmaceuticals, Inc. (www.rigel.com)
Rigel's mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. Rigel has identified three lead product development programs: mast cell inhibition to treat immunologic diseases such as asthma/allergy and autoimmune disorders, antiviral agents to treat hepatitis C, and ligases, a new class of cancer drug targets. Rigel has begun clinical testing of its first product candidate, R112, for allergic rhinitis, and plans to begin clinical trials of three additional drug candidates, for the treatment of hepatitis C, rheumatoid arthritis, and asthma by the end of 2004.

This press release contains "forward-looking" statements, including statements about research and development projects. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "plans", "intends" and similar expressions are intended to identify these forward-looking statements. There are a number of important factors that could cause Rigel's results to differ materially from those indicated by these forward-looking statements, including risks associated with the timing and success of research projects, clinical trials and the commercialization of product candidates, as well as other risks, detailed from time to time in Rigel's SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2003 and Annual Report on Form 10-K, as amended, for the year ended December 31, 2002. Rigel does not undertake any obligation to update forward-looking statements.

BioMed Central

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System 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.