Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the immunological synapse (P6286)

Abstract Mutations of the common cytokine receptor gamma chain (gc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although these lineages are restored by stem cell therapy, residual immune defects are observed that may result from a selective persistence of gc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed gc to protective immune responses. We examined the importance of gc for myeloid lineage dendritic cell (DC) function, and show that DC-expressed gc is required for effective antigen-induced CD4+ T cell activation. Using a novel lipid bilayer system mimicking T cell interaction, we observed that gc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Ra colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on expression of gc in DC. These findings reveal a novel mechanism for recruitment of DC IL-15/IL-15Ra complexes to the immune synapse, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition.