FUNCTIONAL ASSOCIATIONS OF CD38 WITH CD3 ON THE T-CELL MEMBRANE

CD38 is a multifunctional membrane surface glycoprotein expressed by d ifferent cells and tissues, including T cells at certain stages of the ir development. Besides its involvement in transmembrane signaling, CD 38 plays a role in cell adhesion processes. Structurally, membrane CD3 8 was reported as presenting lateral associations with molecules invol ved in recognition and signaling, namely with the TCR/CD3 complex in T cells. Here we report that ligation of CD38 by agonistic and non-agon istic monoclonal antibodies exerts different effects on T cells, the f ormer inducing down-modulation of the associated molecules, probably t hrough a protein kinase C-dependent mechanism. This observation suppor ts the view that the reduced expression of TCR/CD3 is secondary to int erplay, with CD38-mediated signaling, which partially overlaps with th e CD3-mediated pathway,. CD3 ligation by monoclonal antibodies leads n ot only to the expected internalization of the TCR/CD3 complex but als o to downmodulation of surface CD38. The results obtained indicate tha t CD38 is closely, associated with the CD3/TCR complex and that co-mod ulation of CD38 with TCR/CD3 is a critical step in signaling processes on T lymphocytes.