Skip to main content
Log in

Endosomal localization of MHC class II-invariant chain complexes

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

CD4-positive T cells recognize foreign antigens displayed on the surface of antigen-presenting cells as small peptides bound to MHC class II molecules. Thus, the ability of antigen-presenting cells to generate these class II-peptide complexes is central to the initiation and regulation of immune responses. Class II predominantly associates with peptides derived from soluble protein antigens that are internalized and degraded within endosomal compartments. It is within these endosomal compartments that class II encounters and binds antigenic peptides. A number of signals have been implicated in directing the intracellular transport of class II to endosomes. These include sequences within class II itself and within the class II-associated invariant chain (Ii).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pelham H: Recycling of proteins between the ER and Golgi complex. Curr Opin Cell Biol 1991;3:585–591.

    Article  PubMed  CAS  Google Scholar 

  2. Bretscher M, Munro S: Cholesterol and the Golgi apparatus. Science 1993;261:1280–1281.

    Article  PubMed  CAS  Google Scholar 

  3. Ferro-Novick S, Novick P: The role of GTP-binding proteins in transport along the exocytic pathway. Annu Rev Cell Biol 1993;9:575–599.

    Article  PubMed  CAS  Google Scholar 

  4. Mayor S, Presley J, Maxfield F: Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. J Cell Biol 1993; 121:1257–1269.

    Article  PubMed  CAS  Google Scholar 

  5. Davis C, Goldstein J, Sudhof T, Anderson R, Russell D, Brown M: Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature 1987;326:760–765.

    Article  PubMed  CAS  Google Scholar 

  6. Tabas I, Myers J, Innerarity T, Xu X, Arnold K, Boyles J, Maxfield F: The influence of particle size and multiple appprotein-receptor interactions on the endocytic targeting of β-VLDL in mouse peritoneal macrophages. Cell Biol 1991;115: 1547–1560.

    Article  CAS  Google Scholar 

  7. Molloy S, Thomas L, VanSlyke J, Stenberg P, Thomas G: Intracellular trafficking and activation of the furin proprotein convertase: Localization to the TGN and recycling from the cell surface. EMBO J 1994;13: 18–33.

    PubMed  CAS  Google Scholar 

  8. Humphrey J, Peters P, Yuan L, Bonifacino J: Localization of TGN38 to the trans-Golgi network: Involvement of a cytoplasmic tyrosine-containing sequence. J Cell Biol 1993; 120:1123–1135.

    Article  PubMed  CAS  Google Scholar 

  9. Neefjes J, Stollorz V, Peters P, Geuze H, Ploegh H: The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route. Cell 1990;61:171–183.

    Article  PubMed  CAS  Google Scholar 

  10. Guagliardi L, Koppelmann B, Blum J, Marks M, Cresswell P, Brodsky F: Colocalization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature 1990;343: 133–139.

    Article  PubMed  CAS  Google Scholar 

  11. Pieters J, Horstmann H, Bakke O, Griffiths G, Lipp J: Intracellular transport and localization of major histocompatibility complex class II molecules and associated invariant chain. J Cell Biol 1991;115:1213–1223.

    Article  PubMed  CAS  Google Scholar 

  12. Romagnoli P, Layet C, Yewdell J, Bakke O, Germain R: Relationship between invariant chain expression and major histocompatibility complex class II transport into early and late endocytic compartments. J Exp Med 1993;177:583–596.

    Article  PubMed  CAS  Google Scholar 

  13. Harding C, Geuze H: Class II MHC molecules are present in macrophage lysosomes and phagolysosomes that function in the phagocytic processing ofListeria monocytogenes for presentation to T cells. J Cell Biol 1992;119:531–542.

    Article  PubMed  CAS  Google Scholar 

  14. Peters P, Neefjes J, Oorschot V, Ploegh H, Geuze H: Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature 1991;349:669–676.

    Article  PubMed  CAS  Google Scholar 

  15. Amigorena S, Drake J, Webster P, Mellman I: Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes. Nature 1994;369: 113–120.

    Article  PubMed  CAS  Google Scholar 

  16. Qiu Y, Xu X, Wandinger-Ness W, Calke D, Pierce S: Separation of subcellular compartments containing distinct functional forms of MHC class II. J Cell Biol 1994;125: 595–605.

    Article  PubMed  CAS  Google Scholar 

  17. Tulp A, Verwoerd D, Dobberstein B, Ploegh H, Pieters J: Isolation and characterization of the intracellular MHC class II compartment. Nature 1994;369:120–126.

    Article  PubMed  CAS  Google Scholar 

  18. West M, Lucocq J, Watts C: Antigen processing and class II MHC peptide-loading compartments in human B-lymphoblastoid lines. Nature 1994;369:147–151.

    Article  PubMed  CAS  Google Scholar 

  19. Calafat J, Nijenhuis M, Janssen H, Tulp A, Dusseljee S, Wubbolts R, Neefjes J: Major histocompatibility complex class II molecules induce the formation of endocytic MIIC-like structures. J Cell Biol 1994;126: 967–977.

    Article  PubMed  CAS  Google Scholar 

  20. Arunachalam B, Lamb C, Cresswell P: Transport properties of free and MHC class II-associated oligomers containing different isoforms of human invariant chain. Int Immunol 1994;6:439–451.

    Article  PubMed  CAS  Google Scholar 

  21. Riberdy J, Avva R, Geuze H, Cresswell P: Transport and intracellular distribution of MHC class II molecules and associated invariant chain in normal and antigen-processing mutant cell lines. J Cell Biol 1994; 126:1225–1237.

    Article  Google Scholar 

  22. Fling S, Arp B, Pious D: HLA-DMA and HLA-DMB genes are both required for MHC class II/peptide complex formation in antigen presenting cells. Nature 1994;368:554–558.

    Article  PubMed  CAS  Google Scholar 

  23. Morris P, Shaman J, Attaya M, Amaya M, Goodman S, Bergman C, Monaco J, Mellins E: An essential role for HLA-DM in antigen presentation by class II MHC molecules. Nature 1994;368:551–554.

    Article  PubMed  CAS  Google Scholar 

  24. Roche P, Teletski C, Stang E, Bakke O, Long E: Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization. Proc Natl Acad Sci USA 1993;90:8581–8585.

    Article  PubMed  CAS  Google Scholar 

  25. Harter C, Mellman I: Transport of the lysosomal membrane glycoprotein lgp120 (lgp-A) to lysosomes does not require appearance on the plasma membrane. J Cell Biol 1992; 117:311–325.

    Article  PubMed  CAS  Google Scholar 

  26. Lamb C, Yewdell P, Bennink J, Cresswell P: Invariant chain targets HLA class II molecules to acidic endosomes containing internalized influenza virus. Proc Natl Acad Sci USA 1991;88:5998–6002.

    Article  PubMed  CAS  Google Scholar 

  27. Chervonsky A, Gordon L, Sant A: A segment of the MHC class II β chain plays a critical role in targeting class II molecules to the endocytic pathway. Int Immunol 1994;6:973–982.

    Article  PubMed  CAS  Google Scholar 

  28. Simonsen A, Momburg F, Drexler J, Hammerling G, Bakke O: Intracellular distribution of the MHC class II molecules and the associated invariant chain in different cell lines. Int Immunol 1993;5:903–917.

    Article  PubMed  CAS  Google Scholar 

  29. Bikoff E, Huang L, Episkopou V, Meerwijk J, Germain R, Robertson E: Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+T cell selection in mice lacking invariant chain. J Exp Med 1993;177: 1699–1712.

    Article  PubMed  CAS  Google Scholar 

  30. Elliott E, Drake J, Amigorena S, Elsemore J, Webster P, Mellman I, Flavell R: The invariant chain is required for intracellular transport and function of major histocompatibility complex class II molecules. J Exp Med 1994;179:681–694.

    Article  PubMed  CAS  Google Scholar 

  31. Viville S, Neefjes J, Lotteau V, Dierich A, Lemeur M, Ploegh H, Benoist C, Mathis D: Mice lacking the MHC class II-associated invariant chain. Cell 1993;72:635–648.

    Article  PubMed  CAS  Google Scholar 

  32. Anderson M, Miller J: Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules. Proc Natl Acad Sci USA 1992;89:2282–2286.

    Article  PubMed  CAS  Google Scholar 

  33. Layet C, Germain R: Invariant chain promotes egress of poorly expressed, haplotype-mismatched class II major histocompatibility complex AαAβ dimers from the endoplasmic reticulum/cis-Golgi compartment. Proc Natl Acad Sci USA 1991;88:2346–2350.

    Article  PubMed  CAS  Google Scholar 

  34. Schaiff W, Hruska K, Bono C, Shuman S, Schwartz B: Invariant chain influences post-translational processing of HLA-DR molecules. J Immunol 1991;147:603–608.

    PubMed  CAS  Google Scholar 

  35. Loss G, Sant A: Invariant chain retains MHC class II molecules in the endocytic pathway. J Immunol 1993;150:3187–3197.

    PubMed  CAS  Google Scholar 

  36. Neefjes JJ, Ploegh HL: Inhibition of endosomal proteolytic activity by leupeptin blocks surface expression of MHC class II molecules and their conversion to SDS resistant αβ heterodimers in endosomes. EMBO J 1992;11:411–416.

    PubMed  CAS  Google Scholar 

  37. Bakke O, Dobberstein B: MHC class II-associated invariant chains contains a sorting signal for endosomal compartments. Cell 1990;63:707–716.

    Article  PubMed  CAS  Google Scholar 

  38. Lotteau V, Teyton L, Peleraux A, Nilsson T, Karlsson L, Schmid S, Quaranta V, Peterson P: Intracellular transport of class II MHC molecules directed by invariant chain. Nature 1990;348:600–605.

    Article  PubMed  CAS  Google Scholar 

  39. Anderson M, Swier K, Arneson L, Miller J: Enhanced antigen presentation in the absence of the invariant chain endosomal localization signal. J Exp Med 1993;178:1959–1969.

    Article  PubMed  CAS  Google Scholar 

  40. Roche P, Teletski C, Karp D, Pinet V, Bakke O, Long E: Stable surface expression of invariant chain prevents peptide presentation by HLA-DR. EMBO J 1992;11:2841–2847.

    PubMed  CAS  Google Scholar 

  41. Odorizzi C, Trowbridge I, Xue L, Hopkins C, Davis C, Collawn J: Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment. J Cell Biol 1994; 126:317–330.

    Article  PubMed  CAS  Google Scholar 

  42. Pieters J, Bakke O, Dobberstein B: The MHC class II-associated invariant chain contains two endosomal targeting signals within its cytoplasmic tail. J Cell Sci 1993;106:831–846.

    PubMed  CAS  Google Scholar 

  43. Letourneur F, Klausner R: A novel di-leucine motif and a tyrosinebased motif independently mediate lysosomal targeting and endocytosis of CD3 chains. Cell 1992;69:1143–1157.

    Article  PubMed  CAS  Google Scholar 

  44. Arneson L, Miller J: Invariant chain multimerization is necessary for efficient endosomal localization of class-invariant chain complexes. Submitted 1994.

  45. Roche P, Marks M, Cresswell P: Formation of a nine subunit complex by HLA class II glycoproteins and the invariant chain. Nature 1991;354:392–394.

    Article  PubMed  CAS  Google Scholar 

  46. Lamb C, Cresswell P: Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes. J Immunol 1992;148:3478–3482.

    PubMed  CAS  Google Scholar 

  47. Nadimi F, Moreno J, Momburg F, Heuser A, Fuchs S, Adorini L, Hammerling G: Antigen presentation of hen egg lysozyme but not ribonuclease A is augmented by the MHC class II associated invariant chain. Eur J Immunol 1991;21:1255–1263.

    Article  PubMed  CAS  Google Scholar 

  48. Peterson M, Miller J: Invariant chain influences the immunological recognition of MHC class II molecules. Nature 1990;345:172–174.

    Article  PubMed  CAS  Google Scholar 

  49. Peterson M, Miller J: Antigen presentation enhanced by the alternatively spliced invariant chain gene product p41. Nature 1992;357: 596–598.

    Article  PubMed  CAS  Google Scholar 

  50. Salamero J, Humbert M, Cosson P, Davoust J: Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules. EMBO J 1990;9:3489–3496.

    PubMed  CAS  Google Scholar 

  51. Stockinger B, Pessara U, Lin R, Habicht J, Grez M, Koch N: A role of Ia-associated invariant chains in antigen processing and presentation. Cell 1989;56:683–689.

    Article  PubMed  CAS  Google Scholar 

  52. Romagnoli P, Germain R: The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy. J Exp Med 1994; 180:1107–1113.

    Article  PubMed  CAS  Google Scholar 

  53. Freisewinkel I, Schneck K, Koch N: The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of peptide eluted from class II polypeptides. Proc Natl Acad Sci USA 1993;90:9703–9706.

    Article  PubMed  CAS  Google Scholar 

  54. Fineschi B, Arneson L, Naujokas M, Miller J: Differential proteolysis of invariant chain trimers containing a single p41 invariant chain component. Submitted 1994.

  55. Klausner R, Lippincott-Schwartz J, Bonifacino J: The T cell antigen receptor: Insights into organelle biology. Annu Rev Cell Biol 1990;6: 403–431.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miller, J. Endosomal localization of MHC class II-invariant chain complexes. Immunol Res 13, 244–252 (1994). https://doi.org/10.1007/BF02935616

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02935616

Key Words

Navigation