New insights to the functional role of the T cell-Antigen Presenting Cell immunological synapse

three innovative and complementary morphological approaches were employed to study the t cell/antigen presenting cell (apc) interaction: (i) high resolution three-dimensional confocal microscopy of the t cell-apc contact site; (ii) time lapse video recording in living t cells of [ca2+]i and changes in distribution of various gfp fusion proteins with tcr/cd3-zcomplex associated- and other signaling components; (iii) measurement of lateral tcr mobility and that of recruited signaling components using techniques based on fluorescence recovery after photo-bleaching. these approaches were combined with biochemical and functional experiments to investigate two principal issues: (a) recruitment and the three-dimensional arrangement of receptors and signaling components at the contact site between human cd4+ t lymphocytes and apcs, (b) structure of the immunological synapse formed at the contact site between cytotoxic t lymphocytes (ctls) and target cells. we discuss evidence indicating that tcr engagement and triggering can occur in the absence of large-scale molecular segregation into the t cell-apc contact site. taken together our results indicate that although not required for tcr engagement and triggering, formation of the is is important to reinforce tcr-mediated signal transduction and achieve full t cell activation.