L-Selectin and ADAM17 in Activation of Virus Specific T-Cells

dc.contributor.advisorAger, Ann
dc.contributor.advisorKnäuper, Vera
dc.contributor.authorAlanazi, Abdullah Saad
dc.date.accessioned2023-07-13T10:56:56Z
dc.date.available2023-07-13T10:56:56Z
dc.date.issued2023-05-25
dc.description.abstractL-selectin (CD62L) is a homing molecule expressed by leukocytes and is involved in the multistep adhesion cascade of leucocyte recruitment from the bloodstream into tissues. It was previously shown that L-selectin is re-expressed and maintained on primed virus-specific CD8+ T-cells and is required for recruitment to virus infected organs and for protective immunity. Understanding how L-selectin re-expression is regulated may have important implications for endogenous responses as well as clinical implications in adoptive T-cell therapies for viral infection treatment and cancer. It is known that ectodomain proteolytic shedding of L-selectin is regulated by ADAM17. Using an in vitro model of B-cell based peptide-MHC presentation to T-cells expressing a SLY-specific TCR revealed that L-selectin and ADAM17 expression can be detected by flow cytometry and western blotting before and after SLY engagement. Pulldown experiments revealed that L-selectin and ADAM17 are not present in a preformed complex in the cell lysate before activation and were not detectable in a complex after TCR engagement. It is therefore still unclear how ADAM17 comes to cleave L-selectin. Following SLY engagement, the released tail of L-selectin was shown to be degraded by either the proteasome or γ-secretase using specific inhibitors of both pathways. This is consistent with previous work which used the same inhibitors but different modes of T-cell activation (anti-CD3/CD28 and PMA). Furthermore, this is in-line with previous work which showed that cleavable L-selectin drives CD25 expression and clonal T-cell expansion during virus infection. The proteolysis product of the L-selectin membrane retained fragment and its function in driving T-cell expansion remains to be determined in future experiments.
dc.format.extent141
dc.identifier.urihttps://hdl.handle.net/20.500.14154/68593
dc.language.isoen
dc.publisherORCA (Online Research Cardiff Cardiff University) & SDL (Saudi Digital Library)
dc.subjectN/A
dc.titleL-Selectin and ADAM17 in Activation of Virus Specific T-Cells
dc.typeThesis
sdl.degree.departmentDivision of Infection and Immunity, School of Medicine
sdl.degree.disciplineViruses and Immunity
sdl.degree.grantorCardiff University
sdl.degree.nameDoctor of Philosophy

Files

Copyright owned by the Saudi Digital Library (SDL) © 2024