| First Author | Mahtani-Patching J | Year | 2011 |
| Journal | Sci Signal | Volume | 4 |
| Issue | 182 | Pages | ra47 |
| PubMed ID | 21775286 | Mgi Jnum | J:259835 |
| Mgi Id | MGI:6142761 | Doi | 10.1126/scisignal.2001765 |
| Citation | Mahtani-Patching J, et al. (2011) PreTCR and TCRgammadelta signal initiation in thymocyte progenitors does not require domains implicated in receptor oligomerization. Sci Signal 4(182):ra47 |
| abstractText | Whether thymocytes adopt an alphabeta or a gammadelta T cell fate in the thymus is determined at the beta selection checkpoint by the relatively weak or strong signals that are delivered by either the pre-T cell receptor (preTCR) or the gammadelta TCR, respectively. Signal initiation at the beta selection checkpoint is thought to be independent of ligand engagement of these receptors. Some reports have suggested that receptor oligomerization, which is thought to be mediated by either the immunoglobulin (Ig)-like domain of the preTCRalpha (pTalpha) chain or the variable domain of TCRdelta, is a unifying mechanism that initiates signaling in early CD4(-)CD8(-) double-negative (DN) thymocyte progenitors. Here, we demonstrate that the extracellular regions of pTalpha and TCRdelta that are implicated in mediating receptor oligomerization were not required for signal initiation from the preTCR or TCRgammadelta. Indeed, a truncated TCRgammadelta that lacked all of its extracellular Ig-like domains still formed a signaling-competent TCR that drove cells through the beta selection checkpoint. These observations suggest that signal initiation in DN thymocytes is simply a consequence of the surface-pairing of TCR chains, with signal strength being a function of the abundances of surface TCRs. Thus, processes that regulate the surface abundances of TCR complexes in DN cells, such as oligomerization-induced endocytosis, would be predicted to have a major influence in determining whether cells adopt an alphabeta versus gammadelta T cell fate. |
