NDLI: Protein kinase C theta regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL.

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Protein kinase C theta regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL.

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Protein kinase C theta regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Norris, Philip J. Beal, Allison M. Varma, Rajat Dustin, Michael L. Sykulev, Yuri Cameron, Thomas O. Anikeeva, Nadia
Description	Country affiliation: United States Author Affiliation: Beal AM ( Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.)
Abstract	Destruction of virus-infected cells by CTL is an extremely sensitive and efficient process. Our previous data suggest that LFA-1-ICAM-1 interactions in the peripheral supramolecular activation cluster (pSMAC) of the immunological synapse mediate formation of a tight adhesion junction that might contribute to the sensitivity of target cell lysis by CTL. Herein, we compared more (CD8(+)) and less (CD4(+)) effective CTL to understand the molecular events that promote efficient target cell lysis. We found that abrogation of the pSMAC formation significantly impaired the ability of CD8(+) but not CD4(+) CTL to lyse target cells despite having no effect of the amount of released granules by both CD8(+) and CD4(+) CTL. Consistent with this, CD4(+) CTL break their synapses more often than do CD8(+) CTL, which leads to the escape of the cytolytic molecules from the interface. CD4(+) CTL treatment with a protein kinase Ctheta inhibitor increases synapse stability and sensitivity of specific target cell lysis. Thus, formation of a stable pSMAC, which is partially controlled by protein kinase Ctheta, functions to confine the released lytic molecules at the synaptic interface and to enhance the effectiveness of target cell lysis.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cytotoxicity Tests, Immunologic Immunological Synapses Enzymology Immunology Isoenzymes Physiology Protein Kinase C T-lymphocytes, Cytotoxic Amino Acid Sequence Antigens, Cd4 Biosynthesis Antigens, Cd8 Cell Adhesion Cell Aggregation Cell Communication Cell Line, Transformed Clone Cells Enzyme Stability Hiv Antigens Metabolism Secretion Influenza A Virus Lymphocyte Activation Molecular Sequence Data Virology Viral Matrix Proteins Comparative Study Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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