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CD28 is the critical T cell costimulatory receptor which provides to the cell the important second activation signal by binding CD80 and CD86 that are expressed by antigen presenting cells. Besides its costimulation role CD28 functions in preventing T cells from anergic hyporesponsive state or from undergoing premature apoptotic cell death. CD28 is also expressed on human fetal NK cells and some NK cell lines, whereas on murine NK cells the CD28 expression is much broader.