Major histocompatibility complex class I protein conformation altered by transmembrane potential changes

Bene, László; Szöllősi, János; Balázs, Margit; Mátyus, László; Gáspár, R.; Ameloot, Marcel; Dale, Robert E.; Damjanovich, Sándor

doi:10.1002/(sici)1097-0320(19970401)27:4<353::aid-cyto6>3.0.co;2-d

Cited by 21 publications

(5 citation statements)

References 33 publications

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“…In turn, activation of ionotropic glutamate receptors is known to increase MHC I expression in neurons by a NF-Bdependent mechanism (174), thereby potentially amplifying antigen presentation and cytotoxic effects by CD8 ϩ T cells. In addition, MHC I protein complexes per se undergo voltage-dependent conformational changes on alteration of the membrane potential (175), which affect the efficiency of antigen presentation, as well as target cell recognition and killing by CD8 ϩ T cells (176). These findings illustrate the complexity of the molecular signaling mechanisms involved in cytotoxic T cell-neuron interactions.…”

Section: And Unpublished Results)mentioning

confidence: 99%

CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

2009

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Cytotoxic CD8(+) T cells are increasingly recognized as key players in various inflammatory and degenerative central nervous system (CNS) disorders. CD8(+) T cells are believed to actively contribute to neural damage in these CNS conditions. Conceptually, one can separate two possible ways that CD8(+) T cells harm neuronal function or integrity: CD8(+) T cells either directly target neurons and their neurites in an antigen- or contact-dependent fashion, or exert their action via "collateral" mechanisms of neuronal damage that might follow destruction of the myelin sheath or glial cells in both the CNS gray and white matter. After introducing clinical examples, in which the putative relevance CD8(+) T cells has been demonstrated, we summarize knowledge on the sequence of initiation and execution of CD8(+) T-cell responses in the CNS. This includes the initial antigen cross-presentation and priming of naive CD8(+) T cells, followed by the invasion, migration, and target-cell recognition of CD8(+) effector T cells in the CNS parenchyma. Moreover, we discuss mechanisms of impaired electrical signaling and cell death of neurons as direct and collateral targets of CD8(+) T cells in the CNS.

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Section: And Unpublished Results)mentioning

confidence: 99%

CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

2009

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“…Thereby, interactions and activity of membrane proteins may also be modulated by the MP. Earlier FRET experiments indicated that the conformation of the MHC I protein altered reversibly upon membrane depolarization (38). Recently, the dipole potential in the plasma membrane was shown to affect the association and signaling of erbB receptor tyrosine kinases (39).…”

Section: Discussionmentioning

confidence: 99%

Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells

Nagy¹,

Mocsár²,

Sebestyén³

et al. 2018

Biophysical Journal

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The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K release from necrotic cells and hypoxia affecting the expression of K channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function. Therefore, we studied the influence of membrane de- and hyperpolarization on the biophysical properties and signaling of interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors, which play important roles in T cell function. We investigated the mobility, clustering, and signaling of these receptors and major histocompatibility complex (MHC) I/II glycoproteins forming coclusters in lipid rafts of T cells. Depolarization by high K buffer or K channel blockers resulted in a decrease in the mobility of IL-2Rα and MHC glycoproteins, as shown by fluorescence correlation spectroscopy, whereas hyperpolarization by the K ionophore valinomycin increased their mobility. Contrary to this, the mobility of IL-15Rα decreased upon both de- and hyperpolarization. These changes in protein mobility are not due to an alteration of membrane fluidity, as evidenced by fluorescence anisotropy measurements. Förster resonance energy transfer measurements showed that most homo- or heteroassociations of IL-2R, IL-15R, and MHC I did not change considerably, either. MP changes modulated signaling by the two cytokines in distinct ways: depolarization caused a significant increase in the IL-2-induced phosphorylation of signal transducer and activator of transcription 5, whereas hyperpolarization evoked a decrease only in the IL-15-induced signal. Our data imply that the MP may be an important modulator of interleukin receptor signaling and dynamics. Enhanced IL-2 signaling in depolarized T cells highly expressing IL-2R may contribute to suppression of antitumor immune surveillance.

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“…On a similar note but looking at the dynamic side, changes in the structure of proteins [a most evident example being those occurring after their interaction with other proteins or those generated by changes in membrane potential (105)], as well as changes in the constitution or thickness of the various lipid regions, can easily cause reshuffling of the components of lipid rafts so that the best steric͞energetic stability is achieved again (106).…”

Section: Static and Dynamic Factors Organizing Membrane Domainsmentioning

confidence: 99%

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Vereb

Szöllősi

Matkó

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

472

385

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The fluid mosaic membrane model proved to be a very useful hypothesis in explaining many, but certainly not all, phenomena taking place in biological membranes. New experimental data show that the compartmentalization of membrane components can be as important for effective signal transduction as is the fluidity of the membrane. In this work, we pay tribute to the Singer-Nicolson model, which is near its 30th anniversary, honoring its basic features, ''mosaicism'' and ''diffusion,'' which predict the interspersion of proteins and lipids and their ability to undergo dynamic rearrangement via Brownian motion. At the same time, modifications based on quantitative data are proposed, highlighting the often genetically predestined, yet flexible, multilevel structure implementing a vast complexity of cellular functions. This new ''dynamically structured mosaic model'' bears the following characteristics: emphasis is shifted from fluidity to mosaicism, which, in our interpretation, means nonrandom codistribution patterns of specific kinds of membrane proteins forming smallscale clusters at the molecular level and large-scale clusters (groups of clusters, islands) at the submicrometer level. The cohesive forces, which maintain these assemblies as principal elements of the membranes, originate from within a microdomain structure, where lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub-and supramembrane (cytoskeletal, extracellular matrix, other cell) effectors, many of them genetically predestined, play equally important roles. The concept of fluidity in the original model now is interpreted as permissiveness of the architecture to continuous, dynamic restructuring of the molecular-and higherlevel clusters according to the needs of the cell and as evoked by the environment.

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Major histocompatibility complex class I protein conformation altered by transmembrane potential changes

Cited by 21 publications

References 33 publications

CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

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Major histocompatibility complex class I protein conformation altered by transmembrane potential changes

Cited by 21 publications

References 33 publications

CD8+T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

CD8+T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Contact Info

Product

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CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability

CD8⁺T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability