Lipid rafts, major histocompatibility complex molecules, and immune regulation

Goebel, Jens; Forrest, Kathy; Flynn, Dustie; Rao, Rakesh; Roszman, Thomas L.

doi:10.1016/s0198-8859(02)00458-5

Cited by 46 publications

(38 citation statements)

References 32 publications

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“…3). Our results confirm data by others on localization of surface MHC II to DRMs/ patched G M 1-containing membranes (12,(15)(16)(17). Other groups have found similar properties for surface MHC II after antibody-mediated cross-linking of this molecule (11,13,14).…”

Section: Discussionsupporting

confidence: 92%

Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading

Karacsonyi

Knorr

Fülbier

et al. 2004

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 92%

Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading

Karacsonyi

Knorr

Fülbier

et al. 2004

Journal of Biological Chemistry

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“…The localization of MHC class I in rafts might appear surprising in view of contradictory data obtained with M and monocytes (44). In B cells, however, MHC class I was found in microdomains and vesicles that are frequently juxtaposed to lipid rafts (45).…”

Section: Discussionmentioning

confidence: 96%

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Jaksits

Bauer

Kriehuber

et al. 2004

The Journal of Immunology

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Their eponymous morphology and unique ability to activate naive T cells are hallmark features of dendritic cells (DCs). Specific properties of the actin cytoskeleton may define both characteristics. In search for regulators that coordinate DC phenotype and function, we observed strongly increased expression of the actin-remodeling GTPases Cdc42 and Rac1 during DC development from human stem cells. Cdc42 and Rac1 are constitutively active in immature DCs, and their activity is further up-regulated by maturational stimuli such as LPS or CD40L. Activation of Rac1 is associated with its rapid recruitment into lipid rafts. Cdc42 is not recruited into rafts, but readily activated by raft-associated moieties. The functional interplay of rafts, GTPases, and cortical actin is further shown by GTPase activation and actin remodeling after pharmacological disruption of lipid rafts and by the loss of the actin-based DC morphology by transfection of dominant-negative Cdc42 and Rac1. Both Cdc42 and Rac1 also control the transport of essential immunostimulatory molecules to the DC surface. Transfection with dominant-negative GTPases led to reduced surface expression of MHC class I and CD86. Consecutively, DCs display a reduced stimulatory capacity for CD8+ T cells, whereas MHC class II-dependent stimulation of CD4+ T cells remains unperturbed. We conclude that Cdc42 and Rac1 signaling controls DC morphology and conditions DCs for efficient CD8+ T cell stimulation.

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“…A recent report from Joshi-Barve et al (72) showed that EtOH treatment interferes with efficient TCR assembly within lipid rafts by down-regulation of Lck, Zap-70, linker for activation of T cells, and phospholipase C phosphorylation and leads to decreased IL-2 gene expression. MHC class II molecules involved in the formation of the immunological synapse between APCs (B cells or monocytes) and T lymphocytes are associated with lipid rafts, and disruption of rafts results in decreased Ag presentation that has been previously described (73,74), similar to deficient Ag presentation after alcohol administration or in vitro treatment (75). It is intriguing that reduced Ag-specific T cell activation by monocytes or dendritic cells was associated with no changes in the levels of surface MHC class II expression in alcohol-treated cells consistent with the possibility that the signaling function rather than the absolute levels of these proteins are affected by EtOH.…”

Section: Lipid Rafts and Immune Receptors: Relevance To Alcohol-inducmentioning

confidence: 87%

TLR4, Ethanol, and Lipid Rafts: A New Mechanism of Ethanol Action with Implications for other Receptor-Mediated Effects

Szabó

Dolganiuc

Dai

et al. 2007

The Journal of Immunology

126

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Ethanol (EtOH) is the most widely abused substance in the United States, and it contributes to well-documented harmful (at high dosages) and beneficial (at low dosages) changes in inflammatory and immune responses. Lipid rafts have been implicated in the regulation and activation of several important receptor complexes in the immune system, including the TLR4 complex. Many questions remain about the precise mechanisms by which rafts regulate the assembly of these receptor complexes. Results summarized in this review indicate that EtOH acts by altering the LPS-induced redistribution of components of the TLR4 complex within the lipid raft and that this is related to changes in actin cytoskeleton rearrangement, receptor clustering, and subsequent signaling. EtOH provides an example of an immunomodulatory drug that acts at least in part by modifying lipid rafts, and it could represent a model to probe the relationships between rafts, receptor complexes, and signaling.

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Lipid rafts, major histocompatibility complex molecules, and immune regulation

Cited by 46 publications

References 32 publications

Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading

Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

TLR4, Ethanol, and Lipid Rafts: A New Mechanism of Ethanol Action with Implications for other Receptor-Mediated Effects

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