Cutting Edge: TCR Ligation Triggers Digital Activation of NF-κB

Kingeter, Lara M.; Paul, Suman; Maynard, Sean K.; Cartwright, Natalia G.; Schaefer, Brian C.

doi:10.4049/jimmunol.1001051

Cited by 67 publications

(70 citation statements)

References 18 publications

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“…It has been proposed that digitization of NF-kB signaling occurs upstream or at the level of the TCR such that only strong TCR ligands will generate efficient signal to induce gene expression (27). Instead of this, the data presented in this article suggest that even weak TCR signals can produce efficient NF-kB signaling that persists during the immune response.…”

Section: Mut T Cells Recover Nf-kb Signaling In Response To Low-affincontrasting

confidence: 45%

Cutting Edge: The Signals for the Generation of T Cell Memory Are Qualitatively Different Depending on TCR Ligand Strength

Knudson

Hamilton

Daniëls

et al. 2013

The Journal of Immunology

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CD8 T cell memory critically contributes to long-term immunity. Both low- and high-affinity TCR signals are able to support the differentiation of memory CD8 T cells. However, it is unclear whether the requirements for memory development change when TCR signal strength is altered. To gain further insight into this question, we used a TCRβ transmembrane domain mutant model that is defective in the generation of memory in response to high-affinity ligands. Surprisingly, lowering TCR signal strength, by stimulation with low-affinity ligands, resulted in normal memory development. Restoration of memory correlated with recovery of TCR-dependent NF-κB signaling. Thus, these data provide novel evidence that the requirements for memory are qualitatively different depending on TCR signal strength.

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Section: Mut T Cells Recover Nf-kb Signaling In Response To Low-affincontrasting

confidence: 45%

Cutting Edge: The Signals for the Generation of T Cell Memory Are Qualitatively Different Depending on TCR Ligand Strength

Knudson

Hamilton

Daniëls

et al. 2013

The Journal of Immunology

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show abstract

“…T cells then initiate bulk membrane movements involving active actin remodeling, spreading, and formation of an extensive contact area within minutes (14,15). This may be viewed as a global event involving the whole cell (16) and a hallmark of analog-to-digital signal processing (17,18). Also, strong evidence supports the hypothesis that extensive morphological changes may act as early reporters of the triggering of a specific activation program (19,20).…”

mentioning

confidence: 68%

T Lymphocytes Sense Antigens within Seconds and Make a Decision within One Minute

Brodovitch

Bongrand

Pierrès

2013

The Journal of Immunology

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Adaptive immune responses are triggered by the rapid and sensitive detection of MHC-bound peptides by TCRs. The kinetics of early TCR/APC contacts are incompletely known. In this study, we used total internal reflection fluorescence microscopy to image human T cell membranes near model surfaces: contact was mediated by mobile protrusions of <0.4 μm diameter. The mean lifetime of contacts with a neutral surface was 8.6 s. Adhesive interactions increased mean contact time to 27.6 s. Additional presence of TCR ligands dramatically decreased contact to 13.7 s, thus evidencing TCR-mediated triggering of a pulling motion within seconds after ligand encounter. After an interaction typically involving 30–40 contacts formed during a 1-min observation period, TCR stimulation triggered a rapid and active cell spreading. Pulling events and cell spreading were mimicked by pharmacological phospholipase Cγ1 activation, and they were prevented by phospholipase Cγ1 inhibition. These results provide a quantitative basis for elucidating the earliest cell response to the detection of foreign Ags.

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“…Previous studies have reported all-or-nothing activation of signaling molecules that control cytokine gene expression, such as NF-κB [5], NFAT1 [6], Ras [7] and ERK [8]. Ras and ERK have been suggested to acquire digital behavior by positive feedback regulation [7,9].…”

mentioning

confidence: 99%