Breakthrough in Understanding of T-Cell Selection for Antigen Reactivity

Research by University of California Irvine (UC Irvine) immunologists reveals new information about how our immune system functions, shedding light on a vital process that determines how the body’s ability to fight infection develops. In the online version of Nature Immunology published on September 28, 2014, neurology professor Dr. Michael Demetriou, postdoctoral scholar Dr. Raymond Zhou, and other Institute for Immunology colleagues describe a critical mechanism underlying how T-cells are created, selected, and released into the bloodstream. A T- cell (image) is a type of blood cell called a lymphocyte that protects the body from infection. T-cell precursors called thymocytes are created in the bone marrow and migrate to the thymus – a walnut-sized organ at the base of the neck – where they are transformed into T-cells. However, very few thymocytes become fully functional T-cells, and in the current study, the Demetriou team gained important new insights into why. As they are transformed into T-cells, thymocytes grow receptors that react to an antigen (any substance provoking an immune response) that’s bound to a small molecule called MHC major histocompatibility complex). If this reaction is too strong or too weak, the thymocyte does not mature into a T-cell. Dr. Demetriou and the others found that the delicate balance determining the proper reactive ability is controlled by glycosylation, a process in which a sugar attaches to a target protein to give the protein stability and form. They saw that changes in the addition of sugars to receptors – including the blocking of glycosylation – during T-cell development profoundly influenced how thymocytes reacted to the MHC-bound antigens and whether they became mature T-cells.
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