A molecular interplay between the signaling components utilized by cytokine receptors, the pre-T cell receptor (pre-TCR), and the T cell receptor (TCR) is presumed to be required for proper regulation of thymocyte development. The earliest intrathymic progenitors are known to depend on cytokine signaling. However, the mechanisms regulating cytokine signaling during thymopoiesis have not been characterized. Moreover, the contribution of cytokine signaling to the maturation of CD4-CD8- thymocytes into CD4+CD8+ thymocytes, mainly controlled by the pre-TCR, is uncertain. Overexpression of SOCS-1, a negative regulator of cytokine signaling, in developing thymocytes resulted in decreased proliferation following pre-TCR signaling, revealing a novel role for cytokine signaling at this developmental stage. Moreover, pre-TCR signaling negatively regulates SOCS-1 expression, establishing a link between the pre-TCR and mechanisms regulating cytokine signaling. During the later stages of thymocyte development, signals delivered by the pre-TCR and TCR assume a dominant regulatory role. Although structurally similar to the TCR, the pre-TCR possesses distinct biological properties. The major difference between these receptors is the presence of the pTalpha chain in the pre-TCR, which is structurally different from the TCRalpha chain present in the TCR. The connecting peptide domain of pTalpha regulates the interaction between the pre-TCR and the TCR&zgr; subunit. In addition, the structural differences between pTalpha and TCRalpha constitute a post-translational regulatory mechanism to prevent the coexpression of pre-TCR and TCR at the cell surface of CD4+CD8+ thymocytes, as pTalpha cannot pair with TCRbeta in the presence of TCRalpha. The competitive advantage of TCRalpha relates to the position of the bridging cysteine residue within its connecting peptide domain. Thus, the structural features of pTalpha regulate the assembly and surface expression of the pre-TCR, and endow it
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.37622 |
| Date | January 2001 |
| Creators | Trop, Sebastien. |
| Contributors | Hugo, Patrice (advisor), Zuniga-Pflucker, Juan Carlos (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001804731, proquestno: NQ70169, Theses scanned by UMI/ProQuest. |
Page generated in 0.0023 seconds