Receptor Regulation

An Engaging Question of T Cell Receptors

Science's STKE  29 Feb 2000:
Vol. 2000, Issue 21, pp. tw4
DOI: 10.1126/stke.2000.21.tw4

Signal desensitization occurs through several mechanisms involving the inhibition of receptors, intracellular signal mediators, or nuclear transcription factors. Cross-linking of the T cell receptor (TCR) leads to receptor activation followed by rapid desensitization. TCR internalization occurs through protein tyrosine kinase-dependent and -independent mechanisms. Although both engaged and nonengaged receptors are internalized, it is not clear whether both unoccupied or activated receptors must be physically associated, or whether other protein factors are required. San José et al. studied T cells that express chimeric CD3ζ proteins that cannot associate with TCR complexes. Cross-linking chimeric CD3ζ caused the internalization of TCR complexes, and TCR engagement led to concomitant internalization of the CD3ζ chimerae. Internalization of engaged TCRs did not depend on cytoplasmic signaling; however, because activation of the chimeric CD3ζ could still cause internalization of the nonengaged TCRs, the authors suggest that nonengaged TCRs may be internalized through a mechanism that requires intracellular signaling.

San José, E., Borroto, A., Niedergang, F., Alcover, A., and Alarcón, B. (2000) Triggering the TCR complex causes the downregulation of nonengaged receptors by a signal transduction-dependent mechanism. Immunity 12: 161-170. [Online Journal]