Homering In on T Cell Activation

In the immune system, T cells are stimulated by signals that emanate from the T cell receptor (TCR) and costimulatory cell surface receptors, most notably CD28. CD28 signals profoundly influence the ensuing immune response--TCR stimulation in the absence of CD28 results in anergy, a state of permanent inactivation. Huang et al . provide evidence that the alternate pathways for a T cell are coordinated by two cytoplasmic scaffolding proteins, Homer2 and Homer3. Absence of these proteins caused unchecked activity of the central cytokine transcriptional regulator NFAT (nuclear factor of activated T cells), up-regulation of cytokine expression, and signs of overt T cell reactivity. Thus, a dynamic decision mechanism dictates whether a T cell will become activated or anergized. G. N. Huang, D. L. Huso, S. Bouyain, J. Tu, K. A. McCorkell, M. J. May, Y. Zhu, M. Lutz, S. Collins, M. Dehoff, S. Kang, K. Whartenby, J. Powell, D. Leahy, P. F. Worley, NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science 319 , 476-481 (2008). [Abstract] [Full Text]