Characterization of proteins associated with the LFA-1 mediated cytoskeletal / signaling complex in locomotory T lymphocytes

Abstract

LFA-1 plays a crucial role in all aspects of T cell locomotion in both immune physiological functions and pathological conditions. T cell locomotion is associated with translocation of protein kinase C isoenzymes β and δ to the MTOC and microtubules. To identify key players in LFA-1 signaling in the locomotory T cells, the in situ immunoprecipitation technique was deployed in this study. This technique is based on single-ligand triggering of T cell locomotion via immobilized motility inducing antibodies to LFA-1, which mimics the effect of natural ligands. A number of protein kinases (PKCε, PKC δ, PKAIIα) as well as key cytoskeletal components (α and γ-tubulin) and the motor protein dynein, all of which play critical roles in the T cell locomotion, have been studied in this work and were found to physically associate with the LFA-1 induced cytoskeletal/signaling complex. Moreover, a potential association between LFA-1 and members of the transcription factor NFκB (IκBα, P65) was also elucidated in this thesis.