Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunological synapse Muñoz, Pilar Mittelbrunn, María de la Fuente, Hortensia Pérez-Martínez, Manuel García Pérez, Angélica Ariza Veguillas, A Malavasi, Fabio Zubiaur, Mercedes Sáncehez Madrid, Francisco Sancho, Jaime During immunologic synapse (IS) formation, human CD38 redistributes to the contact area of T cell–antigen-presenting cell (APC) conjugates in an antigendependent manner. Confocal microscopy showed that CD38 preferentially accumulated along the contact zone, whereas CD3- redistributed toward the central zone of the IS. APC conjugates with human T cells or B cells transiently expressing CD38–green fluorescent protein revealed the presence of 2 distinct pools of CD38, one localized at the cell membrane and the other in recycling endosomes. Both pools were recruited to the T/APC contact sites and required antigen-pulsed APCs. The process appeared more efficient in T cells than in APCs. CD38 was actively recruited at the IS of T cells by means of Lck-mediated signals. Overexpression of CD38 in T cells increased the levels of antigen-induced intracellular calcium release. Opposite results were obtained by down-regulating surface CD38 expression by means of CD38 siRNA. CD38 blockade in influenza HA-specific T cells inhibited IL-2 and IFN- production, PKC phosphorylation at Thr538, and PKC recruitment to the IS induced by antigen-pulsed APCs. These results reveal a new role for CD38 in modulating antigen-mediated T-cell responses during IS formation. 2025-01-16T08:55:42Z 2025-01-16T08:55:42Z 2008 journal article https://hdl.handle.net/10481/99336 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License