Use this URL to cite or link to this record in EThOS:
Title: Regulation of T cell migration by the guanidine exchange factor Vav1
Author: David, Rachel
ISNI:       0000 0001 3406 9338
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
Availability of Full Text:
Access from EThOS:
Access from Institution:
T cell migration to sites of inflammation is an essential step of an effective immune response. T cell recruitment is enhanced by the recognition of their cognate antigen presented by the endothelium and their retention in the tissue is controlled by resident antigen presenting cells. Vav1 is a guanidine exchange factor for RhoGTPases that is activated through TCR signalling and is important for the cytoskeletal re-arrangements occurring during T cell activation and migration. In this study we have investigated the role of Vav1 in the recruitment and retention of antigen-specific T cells to sites of inflammation. HY-specific Ab-restricted WT and Vav1-/- T cells were generated and fully characterised for specificity and expression of migration-related markers. Vav1-/- T cells showed defects in adhesion, migration in response to ICAM-1, CXCL12 and CXCL10 and increased migratory speed in in vitro assays. Despite displaying defective motility in vitro, both constitutive migration and recruitment of Vav1-/- T cells to antigenic sites occurred normally. However, retention of Vav-1-/- T cells into antigenic tissue was profoundly impaired. This may be due to the inability by Vav-1-/- T cells to respond to ‘stop’ signals delivered by co-engagement of TCR and CD28. In contrast to recent reports on wild type T cells, Vav1-/- T cell migration and retention to sites of inflammation was not affected by engagement of the co-stimulatory molecule CD28, suggesting that Vav-1 recruitment during CD28-mediated signalling is instrumental for Vav-1-mediated regulation of T cell traffic
Supervisor: Marelli-Berg, Federica ; Tybulewicz, Victor Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral