ArticleProceedings of the National Academy of Sciences of the United States of America2006
Differential requirement for Lck during primary and memory CD8+ T cell responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming.Proceedings of the National Academy of Sciences of the United States of America · 2012Trial
- Deciphering the deterministic role of TCR signaling in T cell fate determination.Frontiers in immunology · 2025Review
- Combined Immunodeficiency Caused by a Novel Nonsense Mutation in LCK.Journal of clinical immunology · 2023Article
- Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection.PLoS biology · 2021Article
- Cell Cycle Entry Control in Naïve and Memory CD8Frontiers in cell and developmental biology · 2021Review
- Clonal expansion of innate and adaptive lymphocytes.Nature reviews. Immunology · 2020Review
- Genetic Diversity, Inbreeding Level, and Genetic Load in Endangered Snub-Nosed Monkeys (Frontiers in genetics · 2020Article
- Hepatitis C virus core protein reduces CD8Immunology · 2018Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- DNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte activation in mice.Nature communications · 2017Article
- Suboptimal T-cell receptor signaling compromises protein translation, ribosome biogenesis, and proliferation of mouse CD8 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection.PLoS pathogens · 2017Article
- IL-12 Signals through the TCR To Support CD8 Innate Immune Responses.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Constitutive Lck Activity Drives Sensitivity Differences between CD8+ Memory T Cell Subsets.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Divide, Conquer, and Sense: CD8Frontiers in immunology · 2016Article
- The Timing of T Cell Priming and Cycling.Frontiers in immunology · 2015Review
- TCR Signaling in T Cell Memory.Frontiers in immunology · 2015Review
- Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation.The Journal of experimental medicine · 2014Article
- N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation.The Journal of experimental medicine · 2013Article
- The requirement of linker for activation of T cells in the primary and memory responses of CD8 T cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
T cell receptor (TCR) signaling mediates cell fate decisions throughout the life of a T cell. The earliest biochemical events during antigen-stimulated TCR signaling include activation of the Src-family protein tyrosine kinase, p56(Lck) (Lck), which is an integral component of the TCR signaling complex by its association with the cytoplasmic tails of CD8 or CD4. CD8 and Lck are obligatory during thymic selection of CD8+ T cells. What remain unknown are when and with what stringency Lck is required for effective TCR-mediated activation and function throughout the life of a mature CD8+ T cell. Using mice that express an inducible Lck transgene in T cells, we have investigated the temporal importance of Lck-mediated TCR signaling in antigen-specific CD8+ T cell responses during acute viral infections. We show that Lck deficiency induced in naive mice abrogated the antigen-specific activation and clonal expansion of CD8+ T cells during a primary response to acute viral infections. Moreover, the magnitude of primary CD8 T cell expansion depended on the duration of Lck-dependent TCR signaling. Quite unexpectedly, however, Lck was dispensable for enhanced functional avidity, maintenance, and reactivation of memory CD8+ T cells in vitro and in vivo. These observations suggest that the TCR signaling apparatus is rewired from an Lck-dependent state in naive CD8+ T cells to an Lck-independent state in memory CD8+ T cells. Less stringent requirements for antigen-specific TCR signaling to activate memory CD8+ T cells could, in part, account for their unique hyperreactivity to antigen, which contributes to accelerated immune control during secondary infections.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.