Introduction of antigen into the body causes antigen specific T cells to divided rapidly and then die. If the innate immune system is stimulated at the same time as the animal is exposed to antigen, fewer of the responding T cells die. This phenomenon is thought to account for the ability of antigen presented by infectious agents such as bacteria and viruses to induce productive immune responses and memory T cells. The route whereby activated T cells die, or are protected from death by innate immunity is not understood. Recent experiments suggest that members of the Bcl-2 family, particularly the pro-apoptotic protein, BAD, might be involved. Activated T cells, whether or not they are destined to die, contain more BAD than resting T cells. Experiments will establish the structure and location of BAD in different types of T cells. Since forms of phosphorylated BAD which are not associated with mitochondria are not lethal for cells, BAD may have different forms and/or distribution in activated T cells with different fates. BAD kills cells by binding to anti-apoptotic Bcl-2 family members such as Bcl-XL and use X-ray crystallography to study the structure of the BAD/Bcl-XL complex.
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