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Localization and Intracellular Transport of MHC Class II Molecules in Bone Marrow-Derived Dendritic Cells

  • P. Pierre
  • S. J. Turley
  • J. Meltzer
  • A. Mirza
  • R. Steinman
  • I. Mellman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

Expression of class II molecules is restricted to certain cell types, including B lymphocytes, dendritic cells (DC) from various tissues (e.g. Langerhans cells from skin) and macrophages. Dendritic cells are a system of potent antigen presenting cells (APC) that are characterized by their strong capacity to stimulate immunologically naive T cells1,2. A key function of DC is thought to be the acquisition of antigens in peripheral tissues and their transport to draining lymph nodes for presentation of the processed peptides to the T lymphocytes. Until recently, the major limitation to study the cell biology of dendritic cells has been the absence of long term cell lines and clones. However, the finding that granulocyte-macrophage colony stimulating factor (GM-CSF)3 promotes growth and maturation of large quantities of DC issued from bone marrow progenitors4 provided us with a tool to study the MHC class II transport and distribution in these important APCs. Antigens must be converted in short peptides and loaded on the major histocompatibility complex (MHC) molecules before they can trigger an immune response5. Class II associated peptides are derived from extracellular proteins or endogenous proteins that have access to the endocytic pathway. Class II molecules associate with the Invariant chain (Ii) in the endoplasmic reticulum (ER)6 and are targeted to the endocytic pathway. Class II molecules accumulate transiently in endocytic compartments designated MHC class II compartment (MIIC)7,8,9 or class II vesicles (CIIV)10,11. CIIV are physically and biochemically distinct from endosomes and lysosomes but do, however, contain early endocytic markers such as transferrin receptor and surface immunoglobulins. MIIC, on the other hand, are depleted of recycling receptors and are enriched in late endocytic markers such as Lamp 1. Bone marrow derived DC were cultivated in presence of GM-CSF and a cell biological analysis was performed at different periods of their development. we have shown that major changes in the distribution of class II molecules can be observed during the maturation of DC. Additionaly, we have characterized a new population of DC, representing an intermediate stage of maturation in which CIIV and MIIC can coexist. This developmental switch is coordinated with changes in the distribution of the invariant chain, as well as a dramatic acceleration of class II transport to the plasma membrane.

Keywords

Dendritic Cell Major Histocompatibility Complex Class Mouse Bone Marrow Endocytic Pathway Invariant Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Fossum, S. Cure. Top. Pathol. 15, 101–124 (1989).CrossRefGoogle Scholar
  2. 2.
    Steinman, R.M. Annual Review of Immunology 9, 271–96 (1991).PubMedCrossRefGoogle Scholar
  3. 3.
    Rasko, J.E. and Gough, N.M. in The Cytokine Handbook, 2nd ed 344–369 (Academic Press Limited, 1994 ).Google Scholar
  4. 4.
    Inaba, K., et al. Journal of Experimental Medicine 176, 1693–702 (1992).PubMedCrossRefGoogle Scholar
  5. 5.
    Mellman, 1., Pierre, R. and Amigorena, S. Cure opin. Cell Biol. 7, 564–572 (1995).Google Scholar
  6. 6.
    Lamb, C.A. and Cresswell, R J. Immunol. 148, 3478–82 (1992).PubMedGoogle Scholar
  7. 7.
    Peters, P.J., Neefjes, J.J., Oorschot, V., Ploegh, H.L. and Geuze, H. J. Nature 349, 669–676 (1991).CrossRefGoogle Scholar
  8. 8.
    Tulp, A., Verwoerd, D., Dobberstein, B., Ploegh, H.L. and Pieters, J. Nature 369, 120–126 (1994).PubMedCrossRefGoogle Scholar
  9. 9.
    Qiu, Y., Xu, X., Wandinger-Ness, A., Dalke, D.P. and Pierce, S.K. J. Cell Biol. 125, 595–6605 (1994).Google Scholar
  10. 10.
    Amigorena, S., Drake, J.R., Webster, R and Mellman, 1. Nature 369, 113–120 (1994).PubMedCrossRefGoogle Scholar
  11. 11.
    West, M.A., Lucocq, J.M. and Watts, C. Nature 369, 147–151 (1994).PubMedCrossRefGoogle Scholar
  12. 12.
    Kleijmeer, M.J., et al. J. Immunol. 154, 5715–5724 (1995).PubMedGoogle Scholar
  13. 13.
    Sanderson, F., et al. Science 266, 1566–1569 (1994).PubMedCrossRefGoogle Scholar
  14. 14.
    Cresswell, P. Cell 84, 505–507 (1996).PubMedCrossRefGoogle Scholar
  15. 15.
    Romagnoli, R. and Germain, R.N. J. Exp. Med. 180, 1107–1113 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    Amigorena, S., et al. J. Exp. Med. 181, 1729–1741 (1995).PubMedCrossRefGoogle Scholar
  17. 17.
    Hammond, C. and Helenius, A. J. Cell Biol. 126, 41–52 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    Romagnoli, R, Layet, C., Yewdell, J., Bakke, O. and Germain, R.N. J. Exp. Med. 177, 583–96 (1993).PubMedCrossRefGoogle Scholar
  19. 19.
    Neefjes, J.J. and Ploegh, H.L. EMBO Journal 11, 411–6 (1992).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • P. Pierre
    • 1
  • S. J. Turley
    • 1
  • J. Meltzer
    • 1
  • A. Mirza
    • 1
  • R. Steinman
    • 2
  • I. Mellman
    • 1
  1. 1.Department of Cell BiologyYale School of MedicineNew HavenUSA
  2. 2.Laboratory of Cellular Physiology and ImmunologyThe Rockefeller UniversityNew YorkUSA

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