G. Vamosi and A. Bodnar contributed equally to this manuscript. These studies were supported by the following grants: OTKA TS40773, T48745, T42618, F46497; T38037; T43061; ETT 602/2003, 603/2003; 524/2004; 532/2004; NATO Life Science and Technology Collaborative Linkage Grant 980200, EU FP6 LSHB-CT-2004-503467; Bolyai Janos Research Fellowships (to G. Vamosi and A. Bodnar) and Bekesi Fellowship (to G. Vereb).





atomic force microscopy


activation-induced cell death


antigen-presenting cell


confocal laser scanning microscopy


central supramolecular activation cluster


cytotoxic T cell


cholera toxin B


epidermal growth factor receptor


endoplasmic reticulum


fluorescence cross-correlation spectroscopy


fluorescence correlation spectroscopy


free heavy chain


fluorescence lifetime imaging microscopy


fluorescence resonance energy transfer


intracellular adhesion molecule






immunological synapse


janus kinase


major histocompatibility complex


nerve growth factor


nuclear magnetic resonance


photobleaching FRET


platelet-derived growth factor




peripheral supramolecular activation cluster


scanning near-field optical microscopy


T-cell receptor


vascular endothelial growth factor


1 S.J. Singer, G.L. Nicolson. The fluid mosaic model of the structure of cell membranes. Science 1972, 175, 720-731.

2 L. D. Frye, M. Edidin. The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons.

3 M. Edidin. Patches and fences: probing for plasma membrane domains. J. Cell Sci. Suppl. 1993, 17, 165-169.

4 M. Edidin. Lipid microdomains in cell surface membranes. Curr. Opin. Struct. Biol. 1997, 7, 528-532.

5 S. Damjanovich, R.J. Gâspâr, C. Pieri. Dynamic receptor superstructures at the plasma membrane. Q. Rev. Biophys. 1997, 30, 67-106.

6 S. Damjanovich, J. Matko, L. Mâtyus, G. Szabo, Jr., J. Szollosi, J.C. Pieri, T. Farkas, R. Gâspâr, Jr. Supramolecular receptor structures in the plasma membrane of lymphocytes revealed by flow cytometric energy transfer, scanning force- and transmission electron-microscopic analyses. Cytometry 1998, 33, 225-233.

7 K. Simons, E. Ikonen. Functional rafts in cell membranes. Nature 1997, 387, 569-572.

8 K. Simons, W. L. Vaz. Model systems, lipid rafts, and cell membranes. Annu. Rev. Biophys. Biomol. Struct. 2004, 33, 269-295.

9 G. Vereb, L. Matyus, L. Bene, G. Panyi, Z. Bacso, M. Balazs, J. Matko, J. Szollosi, R. Jr. Gaspar, S. Damjanovich. Plasma membrane bound macromolecules are dynamically aggregated to form nonrandom co-distribution patterns of selected functional elements. Do pattern recognition processes govern antigen presentation and intercellular interactions? J. Mol. Recognit. 1995, 8, 237-246.

10 M. Edidin. Shrinking patches and slippery rafts: scales of domains in the plasma membrane. Trends Cell Biol. 2001, 11, 492-496.

11 G. Vereb, J. Szollosi, J. Matko, P. Nagy, T. Farkas, L. Vigh, L. Matyus, T.A. Waldmann, S. Damjanovich. Dynamic, yet structured: The cell membrane three decades after the Singer-Nicolson model. Proc. Natl. Acad. Sci. USA 2003, 100, 8053-8058.

12 S. Damjanovich, B. Somogyi, L. Tron. Macromolecular dynamics and information transfer. Adv. Physiol. Sci. 1981, 30, 9-15.

13 J. Matko, J. Szollosi. Landing of immune receptors and signal proteins on lipid rafts: a safe way to be spatio-temporally coordinated? Immunol. Lett. 2002, 82, 3-15.

14 R. Zidovetzki, Y. Yarden, J. Schlessinger, T.M. Jovin. Rotational diffusion of epider mal growth factor complexed to cell surface receptors reflects rapid microaggregation and endocytosis of occupied receptors. Proc. Natl. Acad. Sci. USA 1981, 78, 6981-6985.

15 T. S. Ramalingam, A. Chakrabarti, M. Edi-din. Interaction of class I human leukocyte antigen (HLA-I) molecules with insulin receptors and its effect on the insulin-signaling cascade. Mol. Biol. Cell. 1997, 8, 2463-2474.

16 J. Reiland, M. Edidin. Chemical cross-linking detects association of insulin receptors with four different class I human leukocyte antigen molecules on cell surfaces. Diabetes 1993, 42, 619-625.

17 S. Damjanovich, L. Matyus, L. Damjano-vich, L. Bene, A. Jenei, J. Matko, R. Gaspar, J. Szollosi. Does mosaicism of the plasma membrane at molecular and higher hierarchical levels in human lymphocytes carry information on the immediate history of cells? Immunol. Lett. 2002, 82, 93-99.

B. Piknova, V. Schram, J.F. Tournier, M. Welby. Lipid domains and lipid/protein interactions in biological membranes. Chem. Phys. Lipids 1994, 73, 139-158.

19 V. Horejsi. The roles of membrane microdomains (rafts) in T cell activation. Immunol. Rev. 2003, 191, 148-164.

20 V. Horejsi. Membrane rafts in immunor-eceptor signaling: new doubts, new proofs? Trends Immunol. 2002, 23, 562-564.

21 D.C. Hoessli, S. Ilangumaran, A. Solter-mann, P.J. Robinson, B. Borisch, U. D. Nasir. Signaling through sphingolipid microdomains of the plasma membrane: the concept of signaling platform. Glycoconj. J. 2000, 17, 191-197.

22 H.A. Lucero, P.W. Robbins. Lipid rafts-protein association and the regulation of protein activity. Arch. Biochem. Biophys. 2004, 426, 208-224.

23 X. L. Yang, W. C. Xiong, L. Mei. Lipid rafts in neuregulin signaling at synapses. Life Sci. 2004, 75, 2495-2504.

24 R. G. Anderson, K. Jacobson. A role for lipid shells in targeting proteins to caveo-lae, rafts, and other lipid domains. Science 2002, 296, 1821-1825.

25 T. Harder, K. Simons. Caveolae, DIGs, and the dynamics of sphingolipid-choles-terol microdomains. Curr. Opin. Cell Biol. 1997, 9, 534-542.

26 D.A. Brown. Interactions between GPI-anchored proteins and membrane lipids. Trends Cell Biol. 1992, 2, 338-343.

27 M. D. Resh. Membrane targeting of lipid modified signal transduction proteins. Subcell. Biochem. 2004, 37, 217-232.

28 M. D. Resh. Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim. Biophys. Acta 1999, 1451, 1-16.

29 W. Rodgers, D. Farris, S. Mishra. Merging complexes: properties of membrane raft assembly during lymphocyte signaling. Trends Immunol. 2005, 26, 97-103.

30 A. Kusumi, Y. Sako. Cell surface organization by the membrane skeleton. Curr. Opin. Cell Biol. 1996, 8, 566-574.

31 M.A. Lemmon, D. M. Engelman. Specificity and promiscuity in membrane helix interactions. Q. Rev. Biophys. 1994, 27, 157-218.

32 Q. Tang, M. Edidin. Vesicle trafficking and cell surface membrane patchiness. Biophys. J. 2001, 81, 196-203.

33 L. A. Gheber, M. Edidin. A model for membrane patchiness: lateral diffusion in the presence of barriers and vesicle traffic. Biophys. J. 1999, 77, 3163-3175.

34 K. Ritchie, A. Kusumi. Role of the membrane skeleton in creation of microdomains. Subcell. Biochem. 2004, 37, 233-245.

35 J. Pawley. Handbook of biological confocal microscopy. Plenum Press, New York, 1995.

36 W.R. Zipfel, R.M. Williams, W.W. Webb. Nonlinear magic: multiphoton microscopy in the biosciences. Nat. Biotechnol. 2003, 21, 1369-1377.

37 M. Edidin, M.C. Zuniga, M.P. Sheetz. Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins. Proc. Natl. Acad. Sci. USA 1994, 91,


38 A. Kusumi, Y. Sako, M. Yamamoto. Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys. J. 1993, 65, 2021-2040.

39 G. Vereb, J. Matko, G. Vamosi, S.M. Ibrahim, E. Magyar, S. Varga, J. Szöllosi,

A. Jenei, R.J. Gaspar, T.A. Waldmann, S. Damjanovich. Cholesterol-dependent clustering of IL-2Ralpha and its colocal-ization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. Proc. Natl. Acad. Sci. USA 2000, 97, 6013-6018.

J. Matko. Exploring membrane microdomains and functional protein clustering in live cells with flow and image cytomet-ric methods. Reviews in Fluorescence, Kluwer Academic/Plenum Publishers, New York, 2004, pp. 105-152.

41 S. Damjanovich, L. Bene, J. Matko, L. Ma-tyus, Z. Krasznai, G. Szabo, C. Pieri, R.J. Gaspar, J. Szöllosi. Two-dimensional receptor patterns in the plasma membrane of cells. A critical evaluation of their identification, origin and information content. Biophys. Chem. 1999, 82, 99-108.

42 J. Szöllosi, S. Damjanovich, L. Matyus. Application of fluorescence resonance energy transfer in the clinical laboratory: routine and research. Cytometry 1998, 34, 159-179.

43 G. Vereb, J. Matko, J. Szöllosi. Cytometry of fluorescence resonance energy transfer. Methods Cell Biol. 2004, 75, 105-152.

44 T. Förster. Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann. Phys. 1948, 2, 55-75.

45 R. M. Clegg. Fluorescence resonance energy transfer (FRET). In: Fluorescence Imaging Spectroscopy and Microscopy, Wiley, John & Sons, Inc., New York, 1996, pp. 179-252.

46 L. Stryer, R. P. Haugland. Energy transfer: a spectroscopic ruler. Proc. Natl. Acad. Sci. USA 1967, 58, 719-726.

47 E. A. Jares-Erijman, T. M. Jovin. FRET imaging. Nat. Biotechnol. 2003, 21, 1387-1395.

48 P. Nagy, G. Vamosi, A. Bodnar, S.J. Lock-ett, J. Szöllosi. Intensity-based energy transfer measurements in digital imaging microscopy. Eur. Biophys. J. 1998, 27, 377-389.

49 P.I. Bastiaens, I.V. Majoul, P.J. Verveer, H.D. Soling, T.M. Jovin. Imaging the in tracellular trafficking and state of the AB5 quaternary structure of cholera toxin. EMBO J. 1996, 15, 4246-4253.

50 G. Vereb, C.K. Meyer, T.M. Jovin, Novel microscope-based approaches for the investigation of protein-protein interactions in signal transduction. In: Interacting Protein Domains, their Role in Signal and Energy Transduction. Springer-Verlag, New York, 1997, pp. 49-52.

51 T.M. Jovin, D.J. Arndt-Jovin, FRET microscopy: digital imaging of fluorescence resonance energy transfer. Application in cell biology. In: Cell Structure and Function by Microspectrofluorometry. Academic Press, San Diego, 1989, pp. 99-117.

52 R.M. Clegg, O. Holub, C. Gohlke. Fluorescence lifetime-resolved imaging: measuring lifetimes in an image. Methods Enzymol. 2003, 360, 509-542.

53 L. Tron, J. Szöllosi, S. Damjanovich, S.H. Helliwell, D.J. Arndt-Jovin, T.M. Jovin. Flow cytometric measurements of fluorescence resonance energy transfer on cell surfaces. Quantitative evaluation of the transfer efficiency on a cell by cell basis. Biophys. J. 1984, 45, 939-946.

54 Z. Sebestyen, P. Nagy, G. Horvath, G. Vamosi, R. Debets, J.W. Gratama, D.R. Alexander, J. Szöllosi. Long wavelength fluorophores and cell-by-cell correction for autofluorescence significantly improves the accuracy of flow cytometric energy transfer measurements on a dual-laser benchtop flow cytometer. Cytometry 2002, 48, 124-135.

55 R. Rigler, E. S. Elson. Fluorescence Correlation Spectroscopy. Theory and Applications. Springer Verlag, Berlin, Heidelberg, New York, Barcelona, Hong Kong, London, Milan, Paris, Singapore, Tokyo, 2001.

56 J. Widengren, Ü. Mets, R. Rigler. Fluorescence correlation spectroscopy of triplet state in solution: A theoretical and experimental study. J. Phys. Chem. 1995, 99, 13368-13379.

57 K. Bacia, I.V. Majoul, P. Schwille. Probing the endocytic pathway in live cells using dual-color fluorescence cross-correlation analysis. Biophys. J. 2002, 83, 1184-1193.

58 T. Weidemann, M. Wachsmuth, M. Tewes, K. Rippe, J. Langowski. Analysis of ligand binding by two-colour fluores cence cross-correlation spectroscopy. Single Molecules 2002, 3, 49-61.

59 S. Damjanovich, G. Vereb, A. Schaper, A. Jenei, J. Matko, J.P. Starink, G.Q. Fox, D.J. Arndt-Jovin, T.M. Jovin. Structural hierarchy in the clustering of HLA class I molecules in the plasma membrane of human lymphoblastoid cells. Proc. Natl. Acad. Sci. USA 1995, 92, 1122-1126.

A. Bodnar, Z. Bacso, C. Pieri, R.J. Gaspar, T. Farkas, S. Damjanovich. HLA class I and II antigens are partially co-clustered in the plasma membrane of human lym-phoblastoid cells. Proc. Natl. Acad. Sci. USA 1997, 94, 7269-7274.

M. Edidin. Domains in cell plasma membranes investigated by near-field scanning optical microscopy. Biophys. J. 1998, 74, 2184-2190.

62 P. Nagy, L. Bene, M. Balazs, W.C. Hyun, S.J. Lockett, N.Y. Chiang, F. Waldman,

B.G. Feuerstein, S. Damjanovich, J. Szöl-losi. EGF-induced redistribution of erbB2 on breast tumor cells: flow and image cy-tometric energy transfer measurements. Cytometry 1998, 32, 120-131.

63 S.K. Bromley, W.R. Burack, K.G. Johnson, K. Somersalo, T. N. Sims, C. Sumen, M.M. Davis, A.S. Shaw, P.M. Allen, M.L. Dustin. The immunological synapse. Annu. Rev. Immunol. 2001, 19, 375396.

64 A. Grakoui, S.K. Bromley, C. Sumen, M.M. Davis, A.S. Shaw, P.M. Allen, M.L. Dustin. The immunological synapse: a molecular machine controlling T cell activation. Science 1999, 285, 221-227.

A. C. Chan, P. M. Allen, A. S. Shaw. T cell receptor signaling precedes immunologi-cal synapse formation. Science 2002, 295, 1539-1542.

66 M. F. Krummel, M. M. Davis. Dynamics of the immunological synapse: finding, establishing and solidifying a connection. Curr. Opin. Immunol. 2002, 14, 66-74.

67 D.M. Davis, M. L. Dustin. What is the importance of the immunological synapse? Trends Immunol. 2004, 25, 323-327.

68 J. Jacobelli, P.G. Andres, J. Boisvert, M.F. Krummel. New views of the immunolog-ical synapse: variations in assembly and function. Curr. Opin. Immunol. 2004, 16, 345-352.

69 A. Trautmann, S. Valitutti. The diversity of immunological synapses. Curr. Opin. Immunol. 2003, 15, 249-254.

70 T. Harder. Lipid raft domains and protein networks in T-cell receptor signal trans-duction. Curr. Opin. Immunol. 2004, 16, 353-359.

71 H.T. He, A. Lellouch, D. Marguet. Lipid rafts and the initiation of T cell receptor signaling. Semin. Immunol. 2005, 17, 23-33.

72 P. Friedl, J. Storim. Diversity in immune-cell interactions: states and functions of the immunological synapse. Trends Cell Biol. 2004, 14, 557-567.

73 A. Kupfer, S.J. Singer. The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytos-keletal reorganizations in the bound T cell as a function of antigen dose. J. Exp. Med. 1989, 170, 1697-1713.

74 C.R. Monks, B.A. Freiberg, H. Kupfer, N. Sciaky, A. Kupfer. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998, 395, 82-86.

75 J.C. Stinchcombe, G. Bossi, S. Booth, G. M. Griffiths. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 2001, 15, 751-761.

76 P. Friedl, E. B. Brocker. TCR triggering on the move: diversity of T-cell interactions with antigen-presenting cells. Immunol. Rev. 2002, 186, 83-89.

M. P. Dierich, J. Szollosi, S. Damjanovich. Lateral organization of the ICAM-1 molecule at the surface of human lympho-blasts: a possible model for its co-distribution with the IL-2 receptor, class I and class II HLA molecules. Eur. J. Immunol. 1994, 24, 2115-2123.

78 L. Bene, A. Bodnar, S. Damjanovich, G. Vamosi, Z. Bacso, J. Aradi, A. Berta, J. Damjanovich. Membrane topography of HLA I, HLA II, and ICAM-1 is affected by IFN-gamma in lipid rafts of uveal melanomas. Biochem. Biophys. Res. Commun. 2004, 322, 678-683.

79 J. Matko, A. Bodnar, G. Vereb, L. Bene, G. Vamosi, G. Szentesi, J. Szollosi, R.

Caspar, V. Horejsi, T.A. Waldmann, S. Damjanovich. CPI-microdomains (membrane rafts) and signaling of the multichain interleukin-2 receptor in human lymphoma/leukemia T cell lines. Eur. J. Biochem. 2002, 269, 1199-1208.

80 P. Smith, I. Morrison, K. Wilson, N. Fernandez, R. Cherry. Anomalous diffusion of major histocompatibility complex class I molecules on HeLa cells determined by single particle tracking. Biophys. J. 1999, 76, 3331-3344.

81 K. Triantafilou, M. Triantafilou, K.M. Wilson, N. Fernandez. Human major histo-compatibility molecules have the intrinsic ability to form homotypic associations. Hum. Immunol. 2000, 61, 585598.

82 A. Chakrabarti, J. Matko, N.A. Rahman, B.C. Barisas, M. Edidin. Self-association of class I major histocompatibility complex molecules in liposome and cell surface membranes. Biochemistry 1992, 31, 7182-7189.

83 J. Matko, Y. Bushkin, T. Wei, M. Edidin. Clustering of class I HLA molecules on the surfaces of activated and transformed human cells. J. Immunol. 1994, 152, 3353-3360.

84 A. Bodnar, Z. Bacso, A. Jenei, T.M. Jovin, M. Edidin, S. Damjanovich, J. Matko. Class I HLA oligomerization at the surface of B cells is controlled by exogenous b2-microglobulin: implications in activation of cytotoxic T lymphocytes. Int. Immunol. 2003, 15, 331-339.

Y. Bushkin. Soluble p2-microglobulin-free class I heavy chains are released from the surface of activated and leukemia cells by a metalloprotease. J. Biol. Chem. 1994, 269, 6689-6694.

86 W. Pickl, W. Holter, J. Stockl, O. Majdic, W. Knapp. Expression of LA45 reactive b2-microglobulin free HLA class I a-chains on activated T cells is regulated by internalization, constitutive and protein kinase C inducible release. Tissue Antigens 1996, 48, 15-21.

87 W. F. Wade, J. H. Freed, M. Edidin. Trans-lational diffusion of class II major histo-compatibility complex molecules is constrained by their cytoplasmic domains.

88 K.M. Wilson, I.E. Morrison, P. R. Smith, N. Fernandez, R.J. Cherry. Single particle tracking of cell-surface HLA-DR molecules using R-phycoerythrin labeled monoclonal antibodies and fluorescence digital imaging. J. Cell Sci. 1996, 109 (Pt8), 2101-2109.

89 J. Szöllosi, S. Damjanovich, M. Balazs, P. Nagy, L. Tron, M.J. Fulwyler, F.M. Brodsky. Physical association between MHC class I and class II molecules detected on the cell surface by flow cytomet-ric energy transfer. J. Immunol. 1989, 143, 208-213.

B. D. Walker, I. Gaidarov, J. H. Keen, Y. Sykulev. Major histocompatibility complex class I-intercellular adhesion mole-cule-1 association on the surface of target cells: implications for antigen presentation to cytotoxic T lymphocytes. Immunology 2004, 113, 460-471.

S. Damjanovich. INF-g rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells. Biochem. Biophys. Res. Commun. 2002, 290, 635640.

92 T. Lebedeva, M. L. Dustin, Y. Sykulev. ICAM-1 co-stimulates target cells to facilitate antigen presentation. Curr. Opin. Immunol. 2005, 17, 251-258.

C. Beeson, H. McConnell, M. Davis. Initiation of signal transduction through the T cell receptor requires the multivalent engagement of peptide/MHC ligands. Immunity 1998, 9, 459-466.

94 J. Cochran, T. Cameron, L. Stern. The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers. Immunity 2000, 12, 241-250.

95 M.A. Daniels, S.C. Jameson. Critical role for CD8 in T cell receptor binding and activation by peptide/major histocompatibil-ity complex multimers. J. Exp. Med. 2000, 191, 335-345.

96 H.A. Anderson, E.M. Hiltbold, P.A. Roche. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat. Immunol. 2000, 1, 156-162.

97 I. Gombos, C. Detre, G. Vamosi, J. Matko. Rafting MHC-II domains in the APC (presynaptic) plasma membrane and the thresholds for T-cell activation and immunological synapse formation. Immunol. Lett. 2004, 92, 117-124.

98 G. Vamosi, A. Bodnar, G. Vereb, A. Jenei, C. K. Goldman, J. Langowski, K. Toth,

L. Matyus, J. Szollosi, T.A. Waldmann, S. Damjanovich. IL-2 and IL-15 receptor a-subunits are coexpressed in a supramo-lecular receptor cluster in lipid rafts of T cells. Proc. Natl. Acad. Sci. USA 2004, 101, 11082-11087.

99 M. Wadehra, H. Su, L.K. Gordon, L. Goodglick, J. Braun. The tetraspan protein EMP2 increases surface expression of class I major histocompatibility complex proteins and susceptibility to CTL-mediated cell death. Clin. Immunol. 2003, 107, 129-136.

100 R.W. Tilghman, R. L. Hoover. E-selectin and ICAM-1 are incorporated into detergent-insoluble membrane domains following clustering in endothelial cells. FEBS Lett. 2002, 525, 83-87.

101 J. Goebel, K. Forrest, D. Flynn, R. Rao, T. L. Roszman. Lipid rafts, major histo-compatibility complex molecules, and immune regulation. Hum. Immunol. 2002, 63, 813-820.

102 N.J. Poloso, P.A. Roche. Association of MHC class II-peptide complexes with plasma membrane lipid microdomains. Curr. Opin. Immunol. 2004, 16, 103-107.

103 E.M. Hiltbold, N.J. Poloso, P.A. Roche. MHC class II-peptide complexes and APC lipid rafts accumulate at the immu-nological synapse. J. Immunol. 2003, 170, 1329-1338.

104 G. Panyi, Z.-F. Sheng, L.-W. Tu, C. Deutsch. C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism. Biophys. J. 1995, 69, 896-904.

105 G. Panyi, C. Deutsch. Assembly and suppression of endogenous Kv1.3 channels in human T cells. J. Gen. Physiol. 1996, 107, 409-420.

106 G. Panyi, G. Vamosi, A. Bodnar, R. Gaspar, S. Damjanovich. Looking through ion channels: recharged concepts in T-cell signaling. Trends Immunol. 2004, 25, 565-569.

107 G. Panyi, Z. Varga, R. Gaspar. Ion channels and lymphocyte activation. Immunol. Lett. 2004, 92, 55-66.

108 R. S. Lewis. Calcium signaling mechanisms in T lymphocytes. Annu. Rev. Immunol. 2001, 19, 497-521.

109 P.C. Biggin, T. Roosild, S. Choe. Potassium channel structure: domain by domain. Curr. Opin. Struct. Biol. 2000, 10, 456-461.

110 G. Panyi, G. Vamosi, Z. Bacso, M. Bag-dany, A. Bodnar, Z. Varga, R. Gaspar, L. Matyus, S. Damjanovich. Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells. Proc. Natl. Acad. Sci. USA 2004, 101, 1285-1290.

111 P. Hajdu, Z. Varga, C. Pieri, G. Panyi, R. Gaspar, Jr. Cholesterol modifies the gating of Kv1.3 in human T lymphocytes. Pflugers Arch. 2003, 445, 674-682.

112 J.R. Martens, K. O'Connell, M. Tamkun. Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts. Trends Pharmacol. Sci. 2004, 25, 16-21.

113 G. Panyi, M. Bagdany, A. Bodnar, G. Vamosi, G. Szentesi, A. Jenei, L. Matyus, S. Varga, T.A. Waldmann, R. Gaspar,

S. Damjanovich. Colocalization and non-random distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes. Proc. Natl. Acad. Sci. USA 2003, 100, 2592-2597.

114 K.G. Chandy, H. Wulff, C. Beeton, M. Pennington, G. A. Gutman, M. D. Caha-lan. K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci. 2004, 25, 280-289.

115 J. Matko. K+ channels and T-cell synapses: the molecular background for efficient immunomodulation is shaping up. Trends Pharmacol. Sci. 2003, 24, 385-389.

116 L. Bene, J. Szollosi, M. Balazs, L. Matyus, R. Gaspar, M. Ameloot, R. E. Dale, S. Damjanovich. Major histocompatibility complex class I protein conformation altered by transmembrane potential changes. Cytometry 1997, 27, 353-357.

117 M. Levite, L. Cahalon, A. Peretz, R. Hershkoviz, A. Sobko, A. Ariel, R. Desai, B. Attali, O. Lider. Extracellular K+ and opening of voltage-gated potassium chan nels activate T cell integrin function: physical and functional association between Kv1.3 channels and pi integrins. J. Exp. Med. 2000, 191, 1167-1176.

118 P. Nagy, L. Matyus, A. Jenei, G. Panyi, S. Varga, J. Matko, J. Szollosi, R. Gaspar, T. M. Jovin, S. Damjanovich. Cell fusion experiments reveal distinctly different association characteristics of cell-surface receptors. J. Cell Sci. 2001, 114, 4063-4071.

119 T.A. Waldmann, S. Dubois, Y. Tagaya. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 2001, 14, 105-110.

120 T.A. Fehniger, M.A. Cooper, M.A. Cali-giuri. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 2002, 13, 169-183.

121 T.A. Fehniger, M.A. Caligiuri. Interleukin 15: biology and relevance to human disease. Blood 2001, 97, 14-32.

122 S. Kondo, A. Shimizu, Y. Saito, M. Ki-noshita, T. Honjo. Molecular basis for two different affinity states of the interleukin 2 receptor: affinity conversion model. Proc. Natl. Acad. Sci. USA 1986, S3, 9026-9029.

123 S. Damjanovich, L. Bene, J. Matko, A. Alileche, C. K. Goldman, S. Sharrow, T.A. Waldmann. Preassembly of interleukin 2 (IL-2) receptor subunits on resting Kit 225 K6 T cells and their modulation by IL-2, IL-7, and IL-15: a fluorescence resonance energy transfer study. Proc. Natl. Acad. Sci USA 1997, 94, 13134-13139.

124 D.M. Eicher, S. Damjanovich, T.A. Waldmann. Oligomerization of IL-2Ra. Cytokine 2002, 17, 82-90.

125 D.C. Hoessli, M. Poincelet, E. Rungger-Brandle. Isolation of high-affinity murine interleukin 2 receptors as detergent-resistant membrane complexes. Eur. J. Immunol. 1990, 20, 1497-1503.

126 M.D. Marmor, M. Julius. Role for lipid rafts in regulating interleukin-2 receptor signaling. Blood 2001, 9S, 1489-1497.

127 J. Goebel, K. Forrest, L. Morford, T. L. Roszman. Differential localization of IL-2-and -15 receptor chains in membrane rafts of human T cells. J. Leukoc. Biol. 2002, 72, 199-206.

128 C. Lamaze, A. Dujeancourt, T. Baba, C.G. Lo, A. Benmerah, A. Dautry-Varsat. Inter-

leukin 2 receptors and detergent-resistant membrane domains define a clathrin-in-dependent endocytic pathway. Mol. Cell 2001, 7, 661-671.

129 L.J. Pike. Growth factor receptors, lipid rafts and caveolae: An evolving story. Bio-chim. Biophys. Acta 2005.

130 P. Nagy, A. Jenei, S. Damjanovich, T.M. Jovin, J. Szollosi. Complexity of signal transduction mediated by ErbB2: clues to the potential of receptor-targeted cancer therapy. Pathol. Oncol. Res. 1999, 5, 255-271.

131 A. Citri, K. B. Skaria, Y. Yarden. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp. Cell Res. 2003, 284, 54-65.

132 Y. Yarden, M.X. Sliwkowski. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol. 2001, 2, 127-137.

133 G. Vereb, P. Nagy, J.W. Park, J. Szollosi. Signaling revealed by mapping molecular interactions: implications for ErbB-tar-geted cancer immunotherapies. Clin. Appl. Immunol. Rev. 2002, 2, 169-186.

134 M.X. Sliwkowski, J.A. Lofgren, G.D. Lewis, T. E. Hotaling, B.M. Fendly, J.A. Fox. Nonclinical studies addressing the mechanism of action of trastuzumab (Hercep-tin). Semin. Oncol. 1999, 26, 60-70.

135 P. Bagossi, G. Horváth, G. Vereb, J. Szollosi, J. Tozsér. Molecular modeling of nearly full-length ErbB2 receptor. Biophys. J. 2005, 88, 1354-1363.

136 E. Tzahar, H. Waterman, X. Chen, G. Lev-kowitz, D. Karunagaran, S. Lavi, B.J. Ratzkin, Y. Yarden. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell. Biol. 1996, 16, 5276-5287.

137 M.X. Sliwkowski, G. Schaefer, R.W. Akita, J.A. Lofgren, V.D. Fitzpatrick, A. Nuijens, B.M. Fendly, R.A. Cerione, R.L. Vandlen, K. L. Carraway, III. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin.

J. Biol. Chem. 1994, 269, 1466114665.

138 T.W. Gadella, Jr., T.M. Jovin. Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine ki-

nase receptor activation. J. Cell Biol. 1995, 129, 1543-1558.

139 P. Nagy, G. Vereb, Z. Sebestyen, G. Hor-vâth, S.J. Lockett, S. Damjanovich, J.W. Park, T.M. Jovin, J. Szollosi. Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2. J. Cell Sci. 2002, 115, 4251-4262.

140 T.W. Gadella, Jr., R.M. Clegg, T.M. Jovin. Fluorescence lifetime imaging microscopy: Pixel-by-pixel analysis of phasemodulation data. Bioimaging 1994, 2, 139-159.

141 P.I. Bastiaens, T.M. Jovin. Microspectro-scopic imaging tracks the intracellular processing of a signal transduction protein: fluorescent-labeled protein kinase C beta I. Proc. Natl. Acad. Sci. USA 1996, 93, 8407-8412.

142 P. Nagy, A. Jenei, A.K. Kirsch, J. Szöllosi, S. Damjanovich, T.M. Jovin. Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy. J. Cell Sci. 1999, 112 (Pt 11), 1733-1741.

143 E. Monson, G. Merritt, S. Smith, J. P. Langmore, R. Kopelman. Implementation of an NSOM system for fluorescence microscopy. Ultramicroscopy 1995, 57, 257-262.

144 A. K. Kirsch, C.K. Meyer, T.M. Jovin, Integration of optical techniques in scanning probe microscopes: the scanning near-field optical microscope (SNOM). In: Proceedings of NATO Advanced Research Workshop: Analytical Use of Fluorescent

Probes in Oncology, Plenum Press, New York, 1996, pp. 317-323.

145 F.G. Giancotti, E. Ruoslahti. Integrin signaling. Science 1999, 285, 1028-1032.

146 S. Miyamoto, H. Teramoto, J. S. Gutkind, K.M. Yamada. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J. Cell Biol. 1996, 135, 1633-1642.

147 F. Wang, V.M. Weaver, O.W. Petersen, C.A. Larabell, S. Dedhar, P. Briand, R. Lupu, M.J. Bissell. Reciprocal interactions between ß1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc. Natl. Acad. Sci. USA 1998, 95, 14821-14826.

148 B. Leitinger, N. Hogg. The involvement of lipid rafts in the regulation of integrin function. J. Cell Sci. 2002, 115, 963-972.

149 M.A. Adelsman, J.B. McCarthy, Y. Shi-mizu. Stimulation of ß1-integrin function by epidermal growth factor and heregu-lin-ß has distinct requirements for erbB2 but a similar dependence on phosphoino-sitide 3-OH kinase. Mol. Biol. Cell 1999, 10, 2861-2878.

150 M. Mocanu, Z. Fazekas, M. Petras, P. Nagy, Z. Sebestyen, J. Isola, J. Timar, J.W. Park, G. Vereb, J. Szollosi. Associations of ErbB2, ß1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines. Cancer Lett. 2005, 227, 201-212.

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook

Post a comment