Role of CD3gamma and CD3delta cytoplasmic domains in cytolytic T lymphocyte functions and TCR/CD3 down-modulation

Autor:	Luton F, Buferne M, Legendre V, Chauvet E, Boyer C, Anne-Marie Schmitt-Verhulst
Rok vydání:	1997
Předmět:	Cytotoxicity Immunologic Cytoplasm Microscopy Confocal Time Factors CD3 Complex Immunology Receptors Antigen T-Cell Down-Regulation Cell Separation Cell Line Mice Inbred C57BL Mice Mice Inbred CBA Animals Tetradecanoylphorbol Acetate Immunology and Allergy Protein Kinase C T-Lymphocytes Cytotoxic
Zdroj:	Europe PubMed Central
ISSN:	1550-6606 0022-1767
DOI:	10.4049/jimmunol.158.9.4162
Popis:	TCR engagement leads to down-modulation of TCR/CD3 complexes from the T cell surface. The importance of this effect in T cell physiology is unknown. Here, we characterized a CTL clone deficient in TCR/CD3 surface expression that had lost both CD3delta and CD3gamma mRNA, allowing us to address the role of these chains in the assembly, signaling, and dynamics of the TCR/CD3 complex. Expression of either CD3delta or CD3gamma alone failed to reconstitute surface expression of the TCR/CD3 complex, but reconstitution with a cytoplasmically truncated CD3delta (delta t) and a native (gamma) or cytoplasmically truncated (gamma t) human CD3gamma led to reexpression of TCR/CD3 complexes in both cases. This indicated that CD3delta and CD3gamma assume specific functions in TCR/CD3 assembly independently of their cytoplasmic domains. The delta t gamma t variant specifically killed target cells, expressed the IFN-gamma gene in response to Ag, and produced TNF-alpha in response to anti-CD3 mAb, but it was affected in CD3 ligand-induced TCR/CD3 down-modulation. Both PMA- and CD3 ligand-induced TCR/CD3 down-modulation were defective in the delta t gamma t variant, whereas the delta t gamma variants were unaffected, and previously described delta gamma t variants were affected only in PMA-induced down-modulation. Specific protein kinase C (PKC) inhibitors indicated that PMA- but not CD3 ligand-induced down-modulation was dependent on PKC activity. Thus, amino acid sequences present in either the CD3delta or CD3gamma cytoplasmic domain control ligand-induced TCR/CD3 down-modulation, and neither these sequences nor this property are required for cytolysis and IFN-gamma gene expression in response to Ag.
Databáze:	OpenAIRE
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