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Low Activation Threshold As a Mechanism for Ligand-Independent Signaling in Pre-T Cells

2003; American Association of Immunologists; Volume: 170; Issue: 6 Linguagem: Inglês

10.4049/jimmunol.170.6.2853

1550-6606

Mariëlle C. Haks, Stanley M. Belkowski, Maria Ciofani, Michele Rhodes, Juliette M. Lefebvre, Sébastien Trop, Patrice Hugo, Juan Carlos Zúñiga‐Pflücker, David L. Wiest,

Erythrocyte Function and Pathophysiology

Abstract 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 TCRα subunit restores development of pTα-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 αβTCR 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 Ca2+ 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.