It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation

Trends Immunol. 2002 Aug;23(8):413-20. doi: 10.1016/s1471-4906(02)02264-0.


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)-kappaB 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-kappaB-dependent transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD28 Antigens / physiology*
  • Humans
  • Isoenzymes / physiology
  • Lymphocyte Activation*
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinase 2
  • MAP Kinase Kinase Kinases / physiology
  • NF-kappa B / physiology*
  • Protein Kinase C / physiology
  • Protein Kinase C-theta
  • Protein-Serine-Threonine Kinases / physiology
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • CD28 Antigens
  • Isoenzymes
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Protein-Serine-Threonine Kinases
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinase 2
  • MAP Kinase Kinase Kinases
  • MAP3K1 protein, human
  • MAP3K2 protein, human