 enriched in CD45, although this will be discussed further below. The distal pole complex was described by Burkhardt and may be important for sequestering specific negative regulators like SHP-1 (Cullinan et al., 2002). TCR microclusters will be discussed at length. Table I outlines the compartments associated with stable, antigen specific T cell-B cell conjugates.
Parallel studies with supported planar bilayers presenting adhesion molecules revealed similar phenomena in which a single adhesion system would establish a cooperative supamolecular cluster and mixed systems would segregate into spatially discrete SMACs. We examined the organization of the CD2-CD58 and LFA-1-ICAM-1 interactions in contacts in Jurkat T cells on planar bilayers containing ICAM-1 and CD58 (Dustin et al., 1998). We proposed that the “specialized junction, cell polarization, and positional stability” of the symmetric contacts were similar to a neural synapse and proposed that stable T-APC interfaces should be defined as “immunological synapses”. A planar bilayer based system using MHC-peptide complexes and LFA-1 fully recapitulated Kupfer’s findings and provided insight into the dynamics of these structures, which were not formed en bloc, but evolved from very distinct early intermediates by an F-actin dependent transport process (Grakoui et al., 1999)(Fig 1). The immunological synapse has an axis of radial symmetry with its center at the cSMAC (Fig 1). At the same time, we can view the synapse as having a direction of polarity along the length of this axis with a proximal and distal pole relative to the APC containing distinct molecules (Fig 1). The function of the immunological synapse pattern is most transparent for cytotoxic T cells where the F-actin free cSMAC serves as a secretory domain and the pSMAC serves as a retaining wall (Beal et al., 2008; Stinchcombe et al., 2006). The importance of directed secretion is supported by studies with human patients with deficiencies in granule transport to the synapse that lead to defects in kil