Identification of Protein Kinases and Protein Phosphatases Involved in CTL Effector Functions. “ON” and “OFF” Signaling and Immunopharmacological Implications
Biochemical studies of cytotoxic T-lymphocyte (CTL) effector functions, the description of molecular requirements, and the enzymes needed for CTL-induced target cell (TC) death are likely to shed light on the mechanisms and individual participants of practically all steps of CTL-TC interactions (Lancki et al., 1986). These mechanisms include conjugate formation, lethal hit delivery, and events leading to TC death. Identification of important regulatory molecules will also provide key targets for immunomodulation and allow for design of specific pharmacological agents.
KeywordsProtein Phosphatase Phorbol Ester Okadaic Acid Granule Exocytosis Serine Esterase
Unable to display preview. Download preview PDF.
- Albert F, Hua C, Truneh A, Pierre M, Schmitt-Verhulst A-M (1985): Distinction between antigen receptor and IL-2 receptor triggering events in the activation of allo-reactive T cell clones with calcium ionophores and phorbol esters. J Immonol 134: 3649–3655Google Scholar
- Gray LS, Gnarra JR, Engelhard VM (1987): Demonstration of a calcium influx in cytolytic T lymphocytes in response to target cell binding. J Immunol 138: 63–69Google Scholar
- Lancki DW, Weiss A, Fitch FW (1986): Requirements for triggering of lysis by cytolytic T lymphocyte clones. J Immunol 138: 3646–3653Google Scholar
- O’Rourke AM, Mesher MF (1988): T-cell receptor-mediated signaling occurs in the absence of inositol phosphate production. J Biol Chem 263: 18594–18597Google Scholar
- Russell JH (1986): Phorbol-ester stimulated lysis of weak and nonspecific target cells by cytotoxic T lymphocytes. J Immunol 136: 23–27Google Scholar
- Schrezenmeier H, Ahnert-Hilger G, Fleischer B (1988): A T-cell receptor associated GTP-binding protein triggers TCR-mediated granule exocytosis in cytotoxic T lymphocytes. J Immunol 141: 3785–3790Google Scholar
- Taffs RE, Redegeld F, Sitkovsky MV (1991): Modulation of the effector functions of cytolytic T-lymphocytes by an inhibitor of serine/threonine phosphatase, okadaic acid. J Immunol 147: 722–729Google Scholar
- Taffs RE, Sitkovsky MV (1991): Granule enzyme exocytosis assay for cytotoxic T lymphocyte activation. In: Current Protocols in Immunology, Coligan J, Kruisbeek AM, Margulies DH, Shevach EM, Strober W, eds. New York: Wiley InterscienceGoogle Scholar
- Takayama H, Trenn G, Humphrey W. Bluestone JA, Henkart PA, Sitkovsky MV (1987a): Antigen receptor —triggered secretion of a trypsin-type esterase from cytotoxic T-lymphocytes. J Immunol 138: 566–569Google Scholar
- Takayama H, Trenn G, Sitkovsky MV (1988): locus of inhibitory action of cAMP-dependent protein kinase in the antigen receptor triggered cytotoxic T-lymphocyte activation pathway. J Biol Chem 263: 2330–2336Google Scholar
- Trenn G, Taffs R, Hohmann R, Kincaid R, Shevach EM, Sitkovsky M (1989): Biochemical characterization of the inhibitory effect of CsA on cytolytic T-lymphocyte effector functions. J Immunol 142: 3796–3802Google Scholar