A properly functioning immune system is a lesson in balance, providing protection against disease without attacking healthy tissue. Work led by St. Jude Children's Research Hospital scientists and published recently in Nature Immunology has identified a mechanism that helps T cells find that sweet spot where the strength of the immune response matches the threat.
The finding offers important insight into the immune response. The work also lays the foundation for advancing understanding and treatment of problems that arise when the system malfunctions, including autoimmune disorders that occur when the immune system targets healthy tissue or chronic infectious diseases and cancer where the immune response is insufficient.
T cells are the white blood cells that are the body's warriors, using a variety of weapons to combat cancer and viral infections. The receptors that extend above and below the cell membrane serve as a communication channel enabling the T cell response to match the threat. The researchers found that a component of the T cell receptor functions like a rheostat, helping to regulate a key aspect of that response the sometimes explosive production of new T cells called proliferation.
"T cells are a double-edged sword, capable of launching a fierce attack to defeat an infection but also wreaking havoc if the response is too robust and results in damaging healthy tissue," said Dario Vignali, Ph.D., vice chair of the St. Jude Department of Immunology and the paper's senior author. "These findings suggest how T cell receptors help to manage the response and possibly guard against complications resulting from an overly aggressive response."
The results highlight the role of binding regions, called immunoreceptor tyrosine-based activation motifs (ITAMs), in orchestrating an appropriate T cell response. ITAMs are located on the receptor components that extend like tails below the surface of the cell membrane, con
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St. Jude Children's Research Hospital