| Popis: |
γδ T cells play a central role in the detection of epithelial stress as a component of the lymphoid stress surveillance response. Despite their implication in a range of conditions, including several cancers, little is known about how they interact with their antigenic targets, particularly the interaction of γδ TCRs with their ligands. In this thesis I used molecular and structural modelling techniques to characterise recognition of an epithelial stress ligand, EphA2, by a Vδ1+ γδ T cell, MAU. This resulted in a tripartite model of recognition, involving coordinated interaction of EphA2 with both the TCR and its cognate A-ephrin ligands on the T cell, and the identification of a surface patch on the ligand binding domain of EphA2 that potentially represents a TCR binding site. I also performed sequence-level TCR repertoire analysis to assess γδ T cell populations in human colon and liver, and explored, the effect of chronic cytomegalovirus infection on the Vδ1+ γδ T cell repertoire, the first such analysis of its kind. These studies suggested the Vδ2negative repertoire in humans is diverse and largely private, but also highlighted a Vγ5Vδ1 population that was selectively detected in cytomegalovirus-seropositive individuals, and may be involved in cytomegalovirus immunity. |
