Cutting edge:: Cytotoxic granule polarization and cytolysis can occur without central supramolecular activation cluster formation in CD8+ effector T cells

The functional implication of molecular segregation within the immunological synapse remains uncertain. We recently reported that effector but not naive TCR transgenic murine CD8(+) T cells formed immunological synapses containing a central supramolecular activation cluster (cSAMC), suggesting that execution of effector functions such as cytolytic activity might be facilitated by the cSMAC structure. We have now explored this hypothesis using two approaches. First, by simultaneously imaging cSAMC formation and mobilization of cytotoxic granules to the synapse, we observed no correlation between the presence of a cSAMC and granule reorientation. Second, we took advantage of the observation that CD28 costimulation markedly enhances cSAMC formation. Granule polarization to the contact site was indistinguishable with B7-1(+) and B7-1(-) target cells, and cytolytic activity against B7-1(+) or B7-1(-) targets was similar and granule-dependent. Together, our results indicate that the formation of a cSAMC is not required for cytolytic activity in CD8(+) effector T cells.