Al-Alwan, Monther M.2014-10-2120032003AAINQ79400http://hdl.handle.net/10222/55900Generation of an antigen-specific immune response is dependent on T cell activation. A fundamental step for productive activation of T cells is the formation of an immunological synapse at the interface between a T cell and an antigen-presenting cell (APC). Previous studies have demonstrated that synapse formation is a dynamic process depending on active rearrangement of the T cell's cytoskeleton. However, the prevailing view in the literature is that the APCs cytoskeleton plays a passive role in this process. This conclusion was derived from studies that used preactivated T cells with surrogate APCs or APCs such as B cells, but the role of the APCs cytoskeleton in this process has not been examined using naive T cells.Activation of naive T cells is a key step in the generation of primary immune responses. In contrast to preactivated T cells that can be stimulated by all APCs, naive T cells can only be efficiently clustered and activated by dendritic cells (DCs). In this study, I used primary cells to evaluate the role of the APCs cytoskeleton during interactions between DCs and resting/naive T cells. The data demonstrates that in contrast to previous studies, DCs form synapses with T cells. This synapse is characterized by polarization of the DC actin cytoskeleton toward the contact point with the T cells. In contrast to T cells, polarization of the DC's cytoskeleton occurs in an antigen-dependent fashion. Most importantly, DC actin cytoskeletal rearrangement, which is mediated via MHC class II ligation, is critical for antigen-dependent T cell binding and activation.The study provides the first evidence of an active role for the APC/DC's cytoskeleton in the establishment of the synapse with naive T cells. This finding has revolutionized the way the synapse may be perceived. A better knowledge of the mechanisms that control formation of the synapse between DCs and naive T cells will increase our understanding of how to regulate the initiation of immune responses in various diseases.Thesis (Ph.D.)--Dalhousie University (Canada), 2003.Biology, Cell.Health Sciences, Immunology.text