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. 1995 Aug 1;182(2):325–334. doi: 10.1084/jem.182.2.325

Major histocompatibility complex class II compartments in human B lymphoblastoid cells are distinct from early endosomes

PMCID: PMC2192145  PMID: 7629497

Abstract

In human B lymphoblastoid cell lines, the majority of major histocompatibility complex (MHC) class II heterodimers are located on the cell surface and in endocytic compartments, while invariant chain (Ii)-associated class II molecules represent biosynthetic intermediates which are present mostly in the endoplasmic reticulum and Golgi complex. To investigate the origin of the MHC class II-positive compartments and their relation to early endosomes, the intracellular distribution of MHC class II molecules and Ii in relation to endocytic tracers was studied in human lymphoblastoid B cells by immunoelectronmicroscopy on ultrathin cryosections. Cross-linking of surface immunoglobulins, followed by a brief period of internalization of the immune complexes, did not alter the intracellular distribution of MHC class II molecules. While early endosomes were abundantly labeled for the cross-linked immunoglobulins, < 1% of total MHC class II molecules were detectable in early endosomes. MHC class II- and Ii- positive structures associated with the trans-Golgi network can be reached by endocytosed bovine serum albumin (BSA)-gold conjugates after 30 min of internalization. Prolonged exposure to BSA-gold allowed visualization of later endocytic compartments, in which a progressive loss of Ii was observed: first the lumenal portion, and then the cytoplasmic portion of Ii escaped detection, culminating in the formation of MHC class II-positive compartments (MIIC) devoid of Ii. The loss of Ii also correlated with a transition from a multivesicular to a multilaminar, electron-dense MIIC. The intracellular compartments in which class II molecules reside (MIIC) are therefore a heterogeneous set of structures, part of the later aspects of the endocytic pathway.

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Selected References

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  1. Amigorena S., Drake J. R., Webster P., Mellman I. Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes. Nature. 1994 May 12;369(6476):113–120. doi: 10.1038/369113a0. [DOI] [PubMed] [Google Scholar]
  2. Amigorena S., Webster P., Drake J., Newcomb J., Cresswell P., Mellman I. Invariant chain cleavage and peptide loading in major histocompatibility complex class II vesicles. J Exp Med. 1995 May 1;181(5):1729–1741. doi: 10.1084/jem.181.5.1729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baron R., Neff L., Brown W., Courtoy P. J., Louvard D., Farquhar M. G. Polarized secretion of lysosomal enzymes: co-distribution of cation-independent mannose-6-phosphate receptors and lysosomal enzymes along the osteoclast exocytic pathway. J Cell Biol. 1988 Jun;106(6):1863–1872. doi: 10.1083/jcb.106.6.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bijlmakers M. J., Benaroch P., Ploegh H. L. Mapping functional regions in the lumenal domain of the class II-associated invariant chain. J Exp Med. 1994 Aug 1;180(2):623–629. doi: 10.1084/jem.180.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brodsky F. M. What's the score? Nature. 1991 Jul 25;352(6333):288–289. doi: 10.1038/352288c0. [DOI] [PubMed] [Google Scholar]
  6. Bénaroch P., Yilla M., Raposo G., Ito K., Miwa K., Geuze H. J., Ploegh H. L. How MHC class II molecules reach the endocytic pathway. EMBO J. 1995 Jan 3;14(1):37–49. doi: 10.1002/j.1460-2075.1995.tb06973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cresswell P., Blum J. S., Kelner D. N., Marks M. S. Biosynthesis and processing of class II histocompatibility antigens. Crit Rev Immunol. 1987;7(1):31–53. [PubMed] [Google Scholar]
  8. Cresswell P. Intracellular class II HLA antigens are accessible to transferrin-neuraminidase conjugates internalized by receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8188–8192. doi: 10.1073/pnas.82.23.8188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davidson H. W., Reid P. A., Lanzavecchia A., Watts C. Processed antigen binds to newly synthesized MHC class II molecules in antigen-specific B lymphocytes. Cell. 1991 Oct 4;67(1):105–116. doi: 10.1016/0092-8674(91)90575-j. [DOI] [PubMed] [Google Scholar]
  10. Davis J. E., Cresswell P. Lack of detectable endocytosis of B lymphocyte MHC class II antigens using an antibody-independent technique. J Immunol. 1990 Feb 1;144(3):990–997. [PubMed] [Google Scholar]
  11. Geuze H. J., Slot J. W., Strous G. J., Hasilik A., von Figura K. Possible pathways for lysosomal enzyme delivery. J Cell Biol. 1985 Dec;101(6):2253–2262. doi: 10.1083/jcb.101.6.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Geuze H. J., Slot J. W., Strous G. J., Lodish H. F., Schwartz A. L. Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis. Cell. 1983 Jan;32(1):277–287. doi: 10.1016/0092-8674(83)90518-4. [DOI] [PubMed] [Google Scholar]
  13. Guagliardi L. E., Koppelman B., Blum J. S., Marks M. S., Cresswell P., Brodsky F. M. Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature. 1990 Jan 11;343(6254):133–139. doi: 10.1038/343133a0. [DOI] [PubMed] [Google Scholar]
  14. Hackett C. J. Antigen presentation. Later for the rendezvous. Nature. 1991 Feb 21;349(6311):655–656. doi: 10.1038/349655a0. [DOI] [PubMed] [Google Scholar]
  15. Harding C. V., Collins D. S., Slot J. W., Geuze H. J., Unanue E. R. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Cell. 1991 Jan 25;64(2):393–401. doi: 10.1016/0092-8674(91)90647-h. [DOI] [PubMed] [Google Scholar]
  16. Harding C. V., Unanue E. R. Antigen processing and intracellular Ia. Possible roles of endocytosis and protein synthesis in Ia function. J Immunol. 1989 Jan 1;142(1):12–19. [PubMed] [Google Scholar]
  17. Harding C. V., Unanue E. R., Slot J. W., Schwartz A. L., Geuze H. J. Functional and ultrastructural evidence for intracellular formation of major histocompatibility complex class II-peptide complexes during antigen processing. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5553–5557. doi: 10.1073/pnas.87.14.5553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hirsch J. G., Fedorko M. E., Cohn Z. A. Vesicle fusion and formation at the surface of pinocytic vacuoles in macrophages. J Cell Biol. 1968 Sep;38(3):629–632. doi: 10.1083/jcb.38.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koch N., Moldenhauer G., Hofmann W. J., Möller P. Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain (CD74). J Immunol. 1991 Oct 15;147(8):2643–2651. [PubMed] [Google Scholar]
  20. Neefjes J. J., Stollorz V., Peters P. J., Geuze H. J., Ploegh H. L. The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route. Cell. 1990 Apr 6;61(1):171–183. doi: 10.1016/0092-8674(90)90224-3. [DOI] [PubMed] [Google Scholar]
  21. Niebling W. L., Pierce S. K. Antigen entry into early endosomes is insufficient for MHC class II processing. J Immunol. 1993 Apr 1;150(7):2687–2697. [PubMed] [Google Scholar]
  22. Peters P. J., Borst J., Oorschot V., Fukuda M., Krähenbühl O., Tschopp J., Slot J. W., Geuze H. J. Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med. 1991 May 1;173(5):1099–1109. doi: 10.1084/jem.173.5.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peters P. J., Neefjes J. J., Oorschot V., Ploegh H. L., Geuze H. J. Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature. 1991 Feb 21;349(6311):669–676. doi: 10.1038/349669a0. [DOI] [PubMed] [Google Scholar]
  24. Reid P. A., Watts C. Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments. Nature. 1990 Aug 16;346(6285):655–657. doi: 10.1038/346655a0. [DOI] [PubMed] [Google Scholar]
  25. Roche P. A., Teletski C. L., Stang E., Bakke O., Long E. O. Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8581–8585. doi: 10.1073/pnas.90.18.8581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. doi: 10.1084/jem.179.4.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Slot J. W., Geuze H. J. A new method of preparing gold probes for multiple-labeling cytochemistry. Eur J Cell Biol. 1985 Jul;38(1):87–93. [PubMed] [Google Scholar]
  28. Stoorvogel W., Geuze H. J., Griffith J. M., Schwartz A. L., Strous G. J. Relations between the intracellular pathways of the receptors for transferrin, asialoglycoprotein, and mannose 6-phosphate in human hepatoma cells. J Cell Biol. 1989 Jun;108(6):2137–2148. doi: 10.1083/jcb.108.6.2137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tulp A., Verwoerd D., Dobberstein B., Ploegh H. L., Pieters J. Isolation and characterization of the intracellular MHC class II compartment. Nature. 1994 May 12;369(6476):120–126. doi: 10.1038/369120a0. [DOI] [PubMed] [Google Scholar]
  30. West M. A., Lucocq J. M., Watts C. Antigen processing and class II MHC peptide-loading compartments in human B-lymphoblastoid cells. Nature. 1994 May 12;369(6476):147–151. doi: 10.1038/369147a0. [DOI] [PubMed] [Google Scholar]

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