Membrane topography of HLA I, HLA II, and ICAM-1 is affected by IFN-γ in lipid rafts of uveal melanomas

Bene, László; Bodnár, Andrea; Damjanovich, Sándor; Vámosi, György; Bacsó, Zsolt; Aradi, J.; Berta, András; Damjanovich, Judit

doi:10.1016/j.bbrc.2004.07.171

Cited by 22 publications

(19 citation statements)

References 30 publications

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“…Perforin binding, on the other hand, appears to involve a calcium-dependent interaction with cell surface phospholipids. The latter may explain the reduced susceptibility of IFN-␥-treated UM cells to permeabilization by perforin, since this cytokine alters the composition of plasma membrane phospholipids in UM cells (49). The relative contribution of different modes of grB and perforin interaction with the target cell membrane in a process of CTL-mediated killing of UM cells needs to be explored further.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Tumor Cell Phenotype by IFN-γ Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes

Hallermalm

Seki

Geer

et al. 2008

The Journal of Immunology

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IFN-γ, a pleiotropic immune regulator, is implicated in both tumor immune surveillance and selection of tumor variants resistant to immune control, i.e., immunoediting. In uveal melanoma patients, elevated serum levels of IFN-γ correlate with the spread of metastasis and represent a negative prognostic marker. Treatment with IFN-γ boosted the MHC class I presentation machinery in uveal melanoma cells but suppressed their MHC class I-restricted CTL lysis. Tumor cells exposed to IFN-γ efficiently activated specific CTL but were less susceptible to permeabilization by perforin and exhibited a decreased capacity to bind and incorporate granzyme B. These results define a novel mechanism of resistance to granule-mediated CTL lysis in human tumors. Furthermore, the data suggest that immunoediting is not limited to genetic or epigenetic changes resulting in stable cellular phenotypes but also involves an inducible modulation of tumor cells in response to a microenvironment associated with immune activation.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Tumor Cell Phenotype by IFN-γ Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes

Hallermalm

Seki

Geer

et al. 2008

The Journal of Immunology

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“…IFN-␥ changed the expression levels of MHC and ICAM-1 molecules and induced rearrangement of their membrane topography in colon carcinoma and uveal melanoma cells [24,26]. Similar to MHC glycoproteins, a high degree of ICAM-1 self-association was found on HUT102 B2 human T-lymphoma cells [25].…”

Section: Supramolecular Complexes Of Mhc I Mhc Ii and Icam-1 Moleculmentioning

confidence: 92%

“…Molecular associations also occur between MHC glycoproteins and ICAM-1 adhesion molecules in different human cell lines, including T-and B-lymphoma as well as in uveal melanoma and colon carcinoma cells [24][25][26]32]. IFN-␥ changed the expression levels of MHC and ICAM-1 molecules and induced rearrangement of their membrane topography in colon carcinoma and uveal melanoma cells [24,26].…”

Section: Supramolecular Complexes Of Mhc I Mhc Ii and Icam-1 Moleculmentioning

confidence: 94%

“…Self-association of class I and class II MHC glycoproteins as well as their hetero-association were detected by FRET at the surface of various human cell types including APCs [24][25][26][27][28][29]. Electron and scanning force microscopic experiments disclosed the presence of larger scale homo-and hetero-clusters of MHC molecules on the order of several tens of nanometers to microns in size [30,31].…”

Section: Supramolecular Complexes Of Mhc I Mhc Ii and Icam-1 Moleculmentioning

confidence: 99%

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The role of supramolecular protein complexes and membrane potential in transmembrane signaling processes of lymphocytes

et al. 2006

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“…MHC class I and II molecules are associated with lipid rafts defined by detergent extraction (Anderson et al, 2000;Goebel et al, 2002;Bene et al, 2004). However, detergent extraction may itself create artifacts of protein lipid interactions (Heerklotz, 2002).…”

Section: Pufas Phase Separation and Protein Functionmentioning

confidence: 99%

Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection

Shaikh

Edidin

2008

Chemistry and Physics of Lipids

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Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen-presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

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Membrane topography of HLA I, HLA II, and ICAM-1 is affected by IFN-γ in lipid rafts of uveal melanomas

Cited by 22 publications

References 30 publications

Modulation of the Tumor Cell Phenotype by IFN-γ Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes

Modulation of the Tumor Cell Phenotype by IFN-γ Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes

The role of supramolecular protein complexes and membrane potential in transmembrane signaling processes of lymphocytes

Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection

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