In contrast to the minor role in cell conjugation, the sustained MHC-TcR binding in allogeneic co-cultures and the presence of SEA boosted the productive DC-mediated HIV-1 trans-infection of CD4+ T cells through the infectious synapse by a mechanism that is strongly associated with the immune activation mediated by mDC through TcR signaling and co-stimulation. The gene discussed is CD4; the disease is infection.