What Controls T Cell Receptor Phosphorylation?

In a study published in Cell, Xu et al. (2008) raised the intriguing possibility that tyrosine residues present in the immunoreceptor tyrosine-based activation motifs (ITAMs) of the cytoplasmic domain of the CD3ɛ subunit of the T cell receptor (TCR) are sequestered in the membrane. Here, they are inaccessible to tyrosine kinases that would otherwise drive signaling. As a consequence, the authors proposed that "triggering" of the TCR—that is, the events leading to phosphorylation of the receptor—must be dependent upon some, as yet undefined, process that liberates the ITAMs from the membrane.