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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Krummey, Scott M. Snow, Andrew L. Larsen, Sasha E. Stinson, Jeffrey R. Katz, Gil |
Description | Author Affiliation: Katz G ( Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.) |
Abstract | Upon TCR restimulation, activated, cycling T cells can undergo a self-regulatory form of apoptosis known as restimulation-induced cell death (RICD). We previously demonstrated that RICD is impaired in T cells from patients with X-linked lymphoproliferative disease, which lack SLAM-associated protein (SAP) expression. Both SAP and the specific SLAM receptor NK, T, and B cell Ag (NTB-A) are required for RICD, but the mechanism by which these molecules promote a strong, proapoptotic signal through the TCR remains unclear. In this article, we show that the Src-family kinase LCK, but not FYN, associates with NTB-A in activated human T cells. This association increased after TCR restimulation in a SAP-dependent manner, requiring both immunoreceptor tyrosine-based switch motifs in the NTB-A cytoplasmic tail. Both NTB-A-associated LCK phosphorylation and kinase activity were enhanced in restimulated T cells, amplifying proximal TCR signaling. In contrast, TCR-induced LCK association with NTB-A, as well as phosphorylation and kinase activity, was reduced in T cells from patients with X-linked lymphoproliferative disease or normal T cells transfected with SAP-specific small interfering RNA, consistent with RICD resistance. Collectively, our data reveal how SAP nucleates a previously unknown signaling complex involving NTB-A and LCK to potentiate RICD of activated human T cells. |
ISSN | 00221767 |
e-ISSN | 15506606 |
Journal | The Journal of Immunology |
Issue Number | 9 |
Volume Number | 192 |
Language | English |
Publisher | The American Association of Immunologists |
Publisher Date | 2014-05-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Antigens, Cd Immunology Apoptosis Intracellular Signaling Peptides And Proteins Lymphocyte Specific Protein Tyrosine Kinase P56(lck) Receptors, Cell Surface T-lymphocytes Metabolism Enzyme-linked Immunosorbent Assay Flow Cytometry Immunoblotting Immunoprecipitation Lymphocyte Activation Rna, Small Interfering Signal Transduction Cytology Transfection Research Support, Non-u.s. Gov't Discipline Immunology |
Content Type | Text |
Resource Type | Article |
Subject | Immunology and Allergy Immunology |
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