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Intercellular transfer of cell-surface proteins is common and can affect many stages of an immune response

Nature Reviews Immunology volume 7, pages 238–243 (2007)Cite this article

Abstract

Cells can extend the limits of their transcriptome by using proteins captured from other cells. Through an exchange of specific proteins, tools and information can be shared to establish integrated communities of cells that are better able to coordinate stages of an immune response. Transferred proteins can also contribute to pathology by allowing, for example, infection of cell types not otherwise infected. Here, I present the case for considering the intercellular transfer of cell-surface proteins between immune cells as commonplace and important.

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Figure 1: Mechanisms for intercellular protein transfer between immune cells.
Figure 2: Potential functions for the intercellular transfer of cell-surface proteins between immune cells.

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References

  1. Hudson, L., Sprent, J., Miller, J. F. & Playfair, J. H. B cell-derived immunoglobulin on activated mouse T lymphocytes. Nature 251, 60–62 (1974).

    Article  CAS  Google Scholar 

  2. Hudson, L. & Sprent, J. Specific adsorption of IgM antibody onto H-2-activated mouse T lymphocytes. J. Exp. Med. 143, 444–449 (1976).

    Article  CAS  Google Scholar 

  3. Bona, C., Robineaux, R., Anteunis, A., Heuclin, C. & Astesano, A. Transfer of antigen from macrophages to lymphocytes. II. Immunological significance of the transfer of lipopolysaccharide. Immunology 24, 831–840 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Sharrow, S. O., Ozato, K. & Sachs, D. H. Phenotypic expression of I-A and I-E/C subregion determinants on murine thymocytes. J. Immunol. 125, 2263–2268 (1980).

    CAS  PubMed  Google Scholar 

  5. Sharrow, S. O., Mathieson, B. J. & Singer, A. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras. J. Immunol. 126, 1327–1335 (1981).

    CAS  PubMed  Google Scholar 

  6. Lorber, M. I., Loken, M. R., Stall, A. M. & Fitch, F. W. I-A antigens on cloned alloreactive murine T lymphocytes are acquired passively. J. Immunol. 128, 2798–2803 (1982).

    CAS  PubMed  Google Scholar 

  7. Huang, J. F. et al. TCR-Mediated internalization of peptide–MHC complexes acquired by T cells. Science 286, 952–954 (1999).

    Article  CAS  Google Scholar 

  8. Arnold, P. Y., Davidian, D. K. & Mannie, M. D. Antigen presentation by T cells: T cell receptor ligation promotes antigen acquisition from professional antigen-presenting cells. Eur. J. Immunol. 27, 3198–3205 (1997).

    Article  CAS  Google Scholar 

  9. Baba, E. et al. Functional CD4 T cells after intercellular molecular transfer of 0X40 ligand. J. Immunol. 167, 875–883 (2001).

    Article  CAS  Google Scholar 

  10. Hwang, I. et al. T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen-presenting cells. J. Exp. Med. 191, 1137–1148 (2000).

    Article  CAS  Google Scholar 

  11. Tatari-Calderone, Z., Semnani, R. T., Nutman, T. B., Schlom, J. & Sabzevari, H. Acquisition of CD80 by human T cells at early stages of activation: functional involvement of CD80 acquisition in T cell to T cell interaction. J. Immunol. 169, 6162–6169 (2002).

    Article  CAS  Google Scholar 

  12. Hudrisier, D., Riond, J., Mazarguil, H., Gairin, J. E. & Joly, E. Cutting edge: CTLs rapidly capture membrane fragments from target cells in a TCR signaling-dependent manner. J. Immunol. 166, 3645–3649 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Brezinschek, R. I., Oppenheimer-Marks, N. & Lipsky, P. E. Activated T cells acquire endothelial cell surface determinants during transendothelial migration. J. Immunol. 162, 1677–1684 (1999).

    CAS  PubMed  Google Scholar 

  15. Carlin, L. M., Eleme, K., McCann, F. E. & Davis, D. M. Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses. J. Exp. Med. 194, 1507–1517 (2001).

    Article  CAS  Google Scholar 

  16. Sjostrom, A. et al. Acquisition of external major histocompatibility complex class I molecules by natural killer cells expressing inhibitory Ly49 receptors. J. Exp. Med. 194, 1519–1530 (2001).

    Article  CAS  Google Scholar 

  17. Zimmer, J., Ioannidis, V. & Held, W. H-2D ligand expression by Ly49A+ natural killer (NK) cells precludes ligand uptake from environmental cells: implications for NK cell function. J. Exp. Med. 194, 1531–1539 (2001).

    Article  CAS  Google Scholar 

  18. Vanherberghen, B. et al. Human and murine inhibitory natural killer cell receptors transfer from natural killer cells to target cells. Proc. Natl Acad. Sci. USA 101, 16873–16878 (2004).

    Article  CAS  Google Scholar 

  19. Fuchs, A., Cella, M., Giurisato, E., Shaw, A. S. & Colonna, M. Cutting edge: CD96 (tactile) promotes NK cell–target cell adhesion by interacting with the poliovirus receptor (CD155). J. Immunol. 172, 3994–3998 (2004).

    Article  CAS  Google Scholar 

  20. Tabiasco, J. et al. Active trans-synaptic capture of membrane fragments by natural killer cells. Eur. J. Immunol. 32, 1502–1508 (2002).

    Article  CAS  Google Scholar 

  21. Espinosa, E., Tabiasco, J., Hudrisier, D. & Fournie, J. J. Synaptic transfer by human γδ T cells stimulated with soluble or cellular antigens. J. Immunol. 168, 6336–6343 (2002).

    Article  CAS  Google Scholar 

  22. Batista, F. D., Iber, D. & Neuberger, M. S. B cells acquire antigen from target cells after synapse formation. Nature 411, 489–494 (2001).

    Article  CAS  Google Scholar 

  23. Fleire, S. J. et al. B cell ligand discrimination through a spreading and contraction response. Science 312, 738–741 (2006).

    Article  CAS  Google Scholar 

  24. Russo, V. et al. Acquisition of intact allogeneic human leukocyte antigen molecules by human dendritic cells. Blood 95, 3473–3477 (2000).

    CAS  PubMed  Google Scholar 

  25. Herrera, O. B. et al. A novel pathway of alloantigen presentation by dendritic cells. J. Immunol. 173, 4828–4837 (2004).

    Article  CAS  Google Scholar 

  26. Cagan, R. L., Kramer, H., Hart, A. C. & Zipursky, S. L. The bride of sevenless and sevenless interaction: internalization of a transmembrane ligand. Cell 69, 393–399 (1992).

    Article  CAS  Google Scholar 

  27. Zimmer, M., Palmer, A., Kohler, J. & Klein, R. EphB–ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion. Nature Cell Biol. 5, 869–878 (2003).

    Article  CAS  Google Scholar 

  28. Anderson, S. M., Yu, G., Giattina, M. & Miller, J. L. Intercellular transfer of a glycosylphosphatidylinositol (GPI)-linked protein: release and uptake of CD4-GPI from recombinant adeno-associated virus-transduced HeLa cells. Proc. Natl Acad. Sci. USA 93, 5894–5898 (1996).

    Article  CAS  Google Scholar 

  29. Stinchcombe, J., Bossi, G. & Griffiths, G. M. Linking albinism and immunity: the secrets of secretory lysosomes. Science 305, 55–59 (2004).

    Article  CAS  Google Scholar 

  30. Huse, M., Lillemeier, B. F., Kuhns, M. S., Chen, D. S. & Davis, M. M. T cells use two directionally distinct pathways for cytokine secretion. Nature Immunol. 7, 247–255 (2006).

    Article  CAS  Google Scholar 

  31. van Niel, G., Porto-Carreiro, I., Simoes, S. & Raposo, G. Exosomes: a common pathway for a specialized function. J. Biochem. (Tokyo) 140, 13–21 (2006).

    Article  CAS  Google Scholar 

  32. Stinchcombe, J. C., Majorovits, E., Bossi, G., Fuller, S. & Griffiths, G. M. Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443, 462–465 (2006).

    Article  CAS  Google Scholar 

  33. Bell, G. I. Models for the specific adhesion of cells to cells. Science 200, 618–627 (1978).

    Article  CAS  Google Scholar 

  34. Groh, V., Wu, J., Yee, C. & Spies, T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419, 734–738 (2002).

    Article  CAS  Google Scholar 

  35. Roda-Navarro, P., Vales-Gomez, M., Chisholm, S. E. & Reyburn, H. T. Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function. Proc. Natl Acad. Sci. USA 103, 11258–11263 (2006).

    Article  CAS  Google Scholar 

  36. Hwang, I. & Sprent, J. Role of the actin cytoskeleton in T cell absorption and internalization of ligands from APC. J. Immunol. 166, 5099–5107 (2001).

    Article  CAS  Google Scholar 

  37. Sprent, J. Swapping molecules during cell–cell interactions. Sci. STKE 2005, pe8 (2005).

    Article  Google Scholar 

  38. Hudrisier, D. & Joly, E. Plasma membrane nibbling: all lymphocytes do it, but why? ELSO gazette 9, 1–5 (2002).

    Google Scholar 

  39. Joly, E. & Hudrisier, D. What is trogocytosis and what is its purpose? Nature Immunol. 4, 815 (2003).

  40. Puaux, A. L. et al. A very rapid and simple assay based on trogocytosis to detect and measure specific T and B cell reactivity by flow cytometry. Eur. J. Immunol. 36, 779–788 (2006).

    Article  CAS  Google Scholar 

  41. Poupot, M. & Fournie, J. J. Spontaneous membrane transfer through homotypic synapses between lymphoma cells. J. Immunol. 171, 2517–2523 (2003).

    Article  CAS  Google Scholar 

  42. Patel, D. M. & Mannie, M. D. Intercellular exchange of class II major histocompatibility complex/peptide complexes is a conserved process that requires activation of T cells but is constitutive in other types of antigen presenting cell. Cell Immunol. 214, 165–172 (2001).

    Article  CAS  Google Scholar 

  43. Patel, D., Arnold, P., White, G., Nardella, J. & Mannie, M. Class II MHC/peptide complexes are released from APC and are acquired by T Cell responders during specific antigen recognition. J. Immunol. 163, 5201–5210 (1999).

    CAS  PubMed  Google Scholar 

  44. Krogsgaard, M. et al. Agonist/endogenous peptide–MHC heterodimers drive T cell activation and sensitivity. Nature 434, 238–243 (2005).

    Article  CAS  Google Scholar 

  45. Wulfing, C. et al. Costimulation and endogenous MHC ligands contribute to T cell recognition. Nature Immunol. 3, 42–47 (2002).

    Article  CAS  Google Scholar 

  46. Hudrisier, D., Riond, J., Garidou, L., Duthoit, C. & Joly, E. T cell activation correlates with an increased proportion of antigen among the materials acquired from target cells. Eur. J. Immunol. 35, 2284–2294 (2005).

    Article  CAS  Google Scholar 

  47. Davis, D. M. Intrigue at the immune synapse. Sci. Am. 294, 48–55 (2006).

    Article  CAS  Google Scholar 

  48. Rustom, A., Saffrich, R., Markovic, I., Walther, P. & Gerdes, H. H. Nanotubular highways for intercellular organelle transport. Science 303, 1007–1010 (2004).

    Article  CAS  Google Scholar 

  49. Onfelt, B., Nedvetzki, S., Yanagi, K. & Davis, D. M. Cutting edge: Membrane nanotubes connect immune cells. J. Immunol. 173, 1511–1513 (2004).

    Article  Google Scholar 

  50. Eriksson, M. et al. Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets. J. Exp. Med. 190, 1005–1012 (1999).

    Article  CAS  Google Scholar 

  51. Watkins, S. C. & Salter, R. D. Functional connectivity between immune cells mediated by tunneling nanotubules. Immunity 23, 309–318 (2005).

    Article  CAS  Google Scholar 

  52. Karlsson, A. et al. Networks of nanotubes and containers. Nature 409, 150–152 (2001).

    Article  CAS  Google Scholar 

  53. Dustin, M. L. et al. Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity. J. Biol. Chem. 272, 30889–30898 (1997).

    Article  CAS  Google Scholar 

  54. Onfelt, B. et al. Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J. Immunol. 177, 8476–8483 (2006).

    Article  Google Scholar 

  55. Hodneland, E. et al. Automated detection of tunneling nanotubes in 3D images. Cytometry A 69, 961–972 (2006).

    Article  Google Scholar 

  56. Roux, A. et al. Role of curvature and phase transition in lipid sorting and fission of membrane tubules. EMBO. J. 24, 1537–1545 (2005).

    Article  CAS  Google Scholar 

  57. Smyth, L. A., Herrera, O. B., Golshayan, D., Lombardi, G. & Lechler, R. I. A novel pathway of antigen presentation by dendritic and endothelial cells: implications for allorecognition and infectious diseases. Transplantation 82, S15–S18 (2006).

    Article  Google Scholar 

  58. Murgia, C., Pritchard, J. K., Kim, S. Y., Fassati, A. & Weiss, R. A. Clonal origin and evolution of a transmissible cancer. Cell 126, 477–487 (2006).

    Article  CAS  Google Scholar 

  59. Dingli, D. & Nowak, M. A. Cancer biology: infectious tumour cells. Nature 443, 35–36 (2006).

    Article  CAS  Google Scholar 

  60. Game, D. S., Rogers, N. J. & Lechler, R. I. Acquisition of HLA-DR and costimulatory molecules by T cells from allogeneic antigen presenting cells. Am. J. Transplant. 5, 1614–1625 (2005).

    Article  CAS  Google Scholar 

  61. Zhou, J., Tagaya, Y., Tolouei-Semnani, R., Schlom, J. & Sabzevari, H. Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs. Blood 105, 3238–3246 (2005).

    Article  CAS  Google Scholar 

  62. Tsang, J. Y., Chai, J. G. & Lechler, R. Antigen presentation by mouse CD4+ T cells involving acquired MHC class II:peptide complexes: another mechanism to limit clonal expansion? Blood 101, 2704–2710 (2003).

    Article  CAS  Google Scholar 

  63. Carlin, L. M. et al. Secretion of IFN-γ and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse. Blood 106, 3874–3879 (2005).

    Article  CAS  Google Scholar 

  64. Lombardi, G., Sidhu, S., Batchelor, R. & Lechler, R. Anergic T cells as suppressor cells in vitro. Science 264, 1587–1589 (1994).

    Article  CAS  Google Scholar 

  65. Nolte-'t Hoen, E. N. et al. Uptake of membrane molecules from T cells endows antigen-presenting cells with novel functional properties. Eur. J. Immunol. 34, 3115–3125 (2004).

    Article  CAS  Google Scholar 

  66. LeMaoult, J. et al. Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells. Blood 31 October 2006 (doi: 10.1182/blood-2006-05-024547).

    Article  CAS  Google Scholar 

  67. Moffett, A. & Loke, C. Immunology of placentation in eutherian mammals. Nature Rev. Immunol. 6, 584–594 (2006).

    Article  CAS  Google Scholar 

  68. Rouas-Freiss, N., Moreau, P., Ferrone, S. & Carosella, E. D. HLA-G proteins in cancer: do they provide tumor cells with an escape mechanism? Cancer Res. 65, 10139–10144 (2005).

    Article  CAS  Google Scholar 

  69. Tabiasco, J. et al. Acquisition of viral receptor by NK cells through immunological synapse. J. Immunol. 170, 5993–5998 (2003).

    Article  CAS  Google Scholar 

  70. Mack, M. et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nature Med. 6, 769–775 (2000).

    Article  CAS  Google Scholar 

  71. Levchenko, A. et al. Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells. Proc. Natl Acad. Sci. USA 102, 1933–1938 (2005).

    Article  CAS  Google Scholar 

  72. Liu, T. et al. Intercellular transfer of the cellular prion protein. J. Biol. Chem. 277, 47671–47678 (2002).

    Article  CAS  Google Scholar 

  73. Doucey, M. A. et al. Cis association of Ly49A with MHC class I restricts natural killer cell inhibition. Nature Immunol. 5, 328–336 (2004).

    Article  CAS  Google Scholar 

  74. Spees, J. L., Olson, S. D., Whitney, M. J. & Prockop, D. J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl Acad. Sci. USA 103, 1283–1288 (2006).

    Article  CAS  Google Scholar 

  75. Romagnoli, P., Hudrisier, D. & van Meerwijk, J. P. Molecular signature of recent thymic selection events on effector and regulatory CD4+ T lymphocytes. J. Immunol. 175, 5751–5758 (2005).

    Article  CAS  Google Scholar 

  76. Merkenschlager, M. Tracing interactions of thymocytes with individual stromal cell partners. Eur. J. Immunol. 26, 892–896 (1996).

    Article  CAS  Google Scholar 

  77. Baluska, F., Volkmann, D. & Barlow, P. W. Cell bodies in a cage. Nature 428, 371 (2004).

  78. Hudrisier, D. & Bongrand, P. Intercellular transfer of antigen-presenting cell determinants onto T cells: molecular mechanisms and biological significance. FASEB J. 16, 477–486 (2002).

    Article  CAS  Google Scholar 

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Acknowledgements

I thank P. Höglund and members of my laboratory for critical reading of the manuscript. I thank G. Williams for influential discussions on the mechanisms involved in the intercellular transfer of cell-surface proteins. I am also grateful to others who have worked with me in this research area, including L. Carlin, P. Eissmann, F. McCann, B. Önfelt and B. Vanherberghen. I am grateful to D. Bacon for helping construct the figures. My laboratory is financed by the Medical Research Council, the Biotechnology and Biological Science Research Council, and a Lister Research Institute Prize Fellowship.

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  1. Daniel M. Davis is at the Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, UK. d.davis@imperial.ac.uk,

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Davis, D. Intercellular transfer of cell-surface proteins is common and can affect many stages of an immune response. Nat Rev Immunol 7, 238–243 (2007). https://doi.org/10.1038/nri2020

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