Itʹs all Rel-ative: NF-κB and CD28 costimulation of T-cell activation

Costimulatory signals complement or modify the signals provided to a lymphocyte through antigen receptors. For productive T-cell activation, the CD28 molecule is apparently the most important, although not the only, costimulatory receptor. CD28 can provide a signal that is at least partially distinct from that delivered by the T cell receptor (TCR)–CD3 complex. Several lines of evidence indicate that the nuclear factor (NF)-κB pathway is perhaps the most relevant biochemical or transcriptional target for the costimulatory activity of CD28. Although many questions remain, recent years have witnessed significant progress in understanding the signal transduction pathways leading from the TCR and CD28 to Rel/NF-κB-dependent transcription.