Functional associations of CD38 with CD3 on the T-cell membrane.
CD38 is a multifunctional membrane surface glycoprotein expressed by different cells and tissues, including T cells at certain stages of their development. Besides its involvement in transmembrane signaling, CD38 play a role in cell adhesion processes. Structurally, membrane CD38 was reported as presenting lateral associations with molecules involved in recognition and signaling, namely with the TCR/CD3 complex in T cells. Here we report that ligation of CD38 by agonistic and non-agonistic monoclonal antibodies exerts different effects on T cells, the former inducing down-modulation of the associated molecules, probably through a protein kinase C-dependent mechanism. This observation supports the view that the reduced expression of TCR/CD3 is secondary to interplay with CD38-mediated signaling, which partially overlaps with the CD3-mediated pathway. CD3 ligation by monoclonal antibodies leads not only to the expected internalization of the TCR/CD3 complex but also to down-modulation of surface CD38. The results obtained indicate that CD38 is closely associated with the CD3/TCR complex and that co-modulation of CD38 with TCR/CD3 is a critical step in signaling processes on T lymphocytes.
Reinis
M
M
Laboratory of Cell Biology, University of Torino Medical School, Italy.
Morra
M
M
Funaro
A
A
Di Primio
R
R
Malavasi
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology; D015536:Down-Regulation; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D019169:Jurkat Cells / Q000737:chemistry / Q000502:physiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007140:Immunoglobulin Fab Fragments; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011493:Protein Kinase C; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate