CD28

CD28 is a costimulatory receptor that is expressed primarily by T cells. CD28 has limited independent signaling capacity; however, when engaged in concert with the T-cell receptor (TcR), CD28 provides a potent signal that increases interleukin 2 (IL2) production, cell cycle progression and survival of T lymphocytes. In addition, CD28 signaling is sufficient to prevent the induction of anergy. Therefore, CD28 has been widely considered to deliver the "second signal" postulated by a number of investigators to be essential for lymphocyte activation. The ligands for CD28 are CD80 and CD86 (also known as B7.1 and B7.2). The expression of CD86, in particular, is increased upon stimulation of B cells, macrophages and dendritic cells. As such, CD28 ensures that T cells respond vigorously to stimulation by antigen presenting cells in the presence of immunological adjuvants such as LPS. CD28 can also transmit signals via the CD80/CD86 proteins in dendritic cells. CD28 has no intrinsic catalytic activity; however, it can recruit intracellular signaling proteins such as phosphoinositide 3-kinase (PI(3)K), Grb2, Itk, Tec and Lck via SH2- and SH3- mediated interactions with specific sequences in the cytoplasmic domain. CD28 can also stimulate the phosphorylation of Vav, Dok, Lck, Itk, Tec, Ship, Akt and Cbl, possibly via kinases that bind the cytoplasmic domain. CD28 signaling can regulate NFκB and AP1 transcription complexes. CD28 costimulation is defective in Bcl-Xγ^-/- mice. Anergy induction is defective in Cbl-b^-/- mice, suggesting that CD28 may prevent anergy by modulating Cbl-b function and/or expression.