| First Author | Haks MC | Year | 2003 |
| Journal | J Immunol | Volume | 170 |
| Issue | 6 | Pages | 2853-61 |
| PubMed ID | 12626535 | Mgi Jnum | J:126301 |
| Mgi Id | MGI:3760964 | Doi | 10.4049/jimmunol.170.6.2853 |
| Citation | Haks MC, et al. (2003) Low activation threshold as a mechanism for ligand-independent signaling in pre-T cells. J Immunol 170(6):2853-61 |
| abstractText | Pre-TCR complexes are thought to signal in a ligand-independent manner because they are constitutively targeted to lipid rafts. We report that ligand-independent signaling is not a unique capability of the pre-TCR complex. Indeed, the TCR alpha subunit restores development of pT alpha-deficient thymocytes to the CD4(+)CD8(+) stage even in the absence of conventional MHC class I and class II ligands. Moreover, we found that pre-TCR and alpha beta TCR complexes exhibit no appreciable difference in their association with lipid rafts, suggesting that ligand-independence is a function of the CD4(-)CD8(-) (DN) thymocytes in which pre-TCR signaling occurs. In agreement, we found that only CD44(-)CD25(+) DN thymocytes (DN3) enabled activation of extracellular signal-regulated kinases by the pre-TCR complex. DN thymocytes also exhibited a lower signaling threshold relative to CD4(+)CD8(+) thymocytes, which was associated with both the markedly elevated lipid raft content of their plasma membranes and more robust capacitative Ca(2+) entry. Taken together these data suggest that cell-autonomous, ligand-independent signaling is primarily a property of the thymocytes in which pre-TCR signaling occurs. |
