Lysosomal cysteine proteases regulate antigen presentation

Nature Reviews Immunology

Volumn 3, Issue 6, 2003, Pages 472-482

  Honey, Karen ^a   Rudensky, Alexander Y ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC PROTEINASE; CATHEPSIN B; CATHEPSIN D; CATHEPSIN F; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; CD4 ANTIGEN; CYSTEINE PROTEINASE; CYTOKINE; EPITOPE; LEUPEPTIN; LYSOSOME ENZYME; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; TUMOR NECROSIS FACTOR; CATHEPSIN; CD1 ANTIGEN; CD1D ANTIGEN;

ANIMAL MODEL; ANTIGEN PRESENTATION; ARTHRITIS; B LYMPHOCYTE; DENDRITIC CELL; ENZYME ACTIVITY; KNOCKOUT MOUSE; LYMPHOID TISSUE; LYSOSOME STORAGE DISEASE; MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; MOUSE; NATURAL KILLER CELL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; THYMOCYTE; ANIMAL; ENZYME ACTIVATION; ENZYMOLOGY; GENE; HUMAN; IMMUNOLOGY; LYSOSOME;

ANIMALS; ANTIGEN PRESENTATION; ANTIGENS, CD1; CATHEPSINS; CYSTEINE ENDOPEPTIDASES; ENZYME ACTIVATION; GENES, MHC CLASS II; HUMANS; LYMPHOID TISSUE; LYSOSOMES; MICE;

EID: 0037805704     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1110     Document Type: Review

References (116)

1. Watts, C. Capture and processing of exogenous antigens for presentation on MHC molecules. Annu. Rev. Immunol. 15, 821-850 (1997).
2. Rock, K. L. & Goldberg, A. L. Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu. Rev. Immunol. 17, 739-779 (1999).
3. Sant, A. J. & Miller, J. MHC class II antigen processing: biology of invariant chain. Curr. Opin. Immunol. 6, 57-63 (1994).
4. Cresswell, P. Invariant chain structure and MHC class II function. Cell 84, 505-507 (1996).
5. Ghosh, P., Amaya, M., Mellins, E. & Wiley, D. C. The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature 378, 457-462 (1995).
6. Morkowski, S. et al. T cell recognition of major histocompatibility complex class II complexes with invariant chain processing intermediates. J. Exp. Med. 182, 1403-1413 (1995).
7. Busch, R., Cloutier, I., Sekaly, R. P. & Hammerling, G. J. Invariant chain protects class II histocompatibility antigens from binding intact polypeptides in the endoplasmic reticulum. EMBO J. 15, 418-428 (1996).
8. 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. USA 90, 8581-8585 (1993).
9. Saudrais, C. et al. Intracellular pathway for the generation of functional MHC class II peptide complexes in immature human dendritic cells. J. Immunol. 160, 2597-2607 (1998).
10. Brachet, V., Pehau-Arnaudet, G., Desaymard, C., Raposo, G. & Amigorena, S. Early endosomes are required for major histocompatibility complex class II transport to peptide-loading compartments. Mol. Biol. Cell 10, 2891-2904 (1999).
11. Bakke, O. & Dobberstein, B. MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell 63, 707-716 (1990).
12. Lotteau, V. et al. Intracellular transport of class II MHC molecules directed by invariant chain. Nature 348, 600-605 (1990).
13. Benaroch, P. et al. How MHC class II molecules reach the endocytic pathway. EMBO J. 14, 37-49 (1995).
14. Kleijmeer, M. J., Morkowski, S., Griffith, J. M., Rudensky, A. Y. & Geuze, H. J. Major histocompatibility complex class II compartments in human and mouse B lymphoblasts represent conventional endocytic compartments. J. Cell Biol. 139, 639-649 (1997).
15. Maric, M. A., Taylor, M. D. & Blum, J. S. Endosomal aspartic proteinases are required for invariant-chain processing. Proc. Natl Acad. Sci. USA 91, 2171-2175 (1994).
16. Riese, R. J. et al. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity 4, 357-366 (1996). This paper uses a chemical inhibitor to show, for the first time, that cathepsin S mediates degradation of the invariant chain (11) in B cells.
17. Maric, M. et al. Defective antigen processing in GILT-free mice. Science 294, 1361-1365 (2001).
18. Haque, M. A. et al. Absence of γ-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes. J. Exp. Med. 195, 1267-1277 (2002).
19. Denzin, L. K. & Cresswell, P. HLA-DM induces CLIP dissociation from MHC class II αβ dimers and facilitates peptide loading. Cell 82, 155-165 (1995).
20. Sherman, M. A., Weber, D. A. & Jensen, P. E. DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide. Immunity 3, 197-205 (1995).
21. Wubbolts, R. et al. Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface. J. Cell Biol. 135, 611-622 (1996).
22. Kleijmeer, M. et al. Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. J. Cell Biol. 155, 53-63 (2001).
23. Chow, A., Toomre, D., Garrett, W. & Mellman, I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 418, 988-994 (2002).
24. Boes, M. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983-988 (2002).
25. Villadangos, J. A. et al. Proteases involved in MHC class II antigen presentation. Immunol. Rev. 172, 109-120 (1999).
26. Nakagawa, T. Y. & Rudensky, A. Y. The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation. Immunol. Rev. 172, 121-129 (1999).
27. Salvesen, G. S. A lysosomal protease enters the death scene. J. Clin. Invest. 107, 21-22 (2001).
28. Reinheckel, T., Deussing, J., Roth, W. & Peters, C. Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice deficient for cathepsin B or cathepsin L. Biol. Chem. 382, 735-741 (2001).
29. + T cell selection and maturation by cathepsin S. Immunity 15, 909-919 (2001).
30. + natural killer T (NKT) cells.
31. McGrath, M. E. The lysosomal cysteine proteases. Annu. Rev. Biophys. Biomol. Struct. 28, 181-204 (1999).
32. Chen, J. M. et al. Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase. J. Biol. Chem. 272, 8090-8098 (1997).
33. Turk, V., Turk, B. & Turk, D. Lysosomal cysteine proteases: facts and opportunities. EMBO J. 20, 4629-4633 (2001).
34. 125I] iodotyrosylalanyldiazomethane as a probe for active cysteine proteinases in human tissues. J. Biochem. 263, 945-949 (1989).
35. Bogyo, M., Verhelst, S., Bellingard-Dubouchaud, V., Toba, S. & Greenbaum, D. Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs. Chem. Biol. 7, 27-38 (2000).
36. Chapman, H. A., Riese, R. J. & Shi, G. P. Emerging roles for cysteine proteases in human biology. Annu. Rev. Physiol. 59, 63-88 (1997).
37. Blum, J. S. & Cresswell, P. Role for intracellular proteases in the processing and transport of class II HLA antigens. Proc. Natl Acad. Sci. USA 85, 3975-3979 (1988).
38. Deussing, J. et al. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc. Natl Acad. Sci. USA 95, 4516-4521 (1998).
39. Villadangos, J. A., Riese, R. J., Peters, C., Chapman, H. A. & Ploegh, H. L. Degradation of mouse invariant chain: roles of cathepsins S and D and the influence of major histocompatibility complex polymorphism. J. Exp. Acad. 186, 549-560 (1997).
40. Riese, R. J. et al. Cathepsin S activity regulates antigen presentation and immunity. J. Clin. Invest. 101, 2351-2363 (1998).
41. Manoury, B. et al. Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone. Immunity 18, 489-498 (2003). The identification of asparagine endopeptidase as a lysosomal protease that can initiate the cleavage of Ii.
42. + T-cell selection is markedly reduced.
43. Nakagawa, T. Y. et al. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity 10, 207-217 (1999).
44. Shi, G. P. et al. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity 10, 197-206 (1999). Together with reference 43, this report uses targeted gene deletion to show that cathepsin S mediates the late stages of Ii degradation in B cells, dendritic cells and macrophages.
45. Driessen, C. et al. Cathepsin S controls the trafficking and maturation of MHC class Ii molecules in dendritic cells. J. Cell Biol. 147, 775-790 (1999).
46. Honey, K. et al. Cathepsin S regulates the expression of cathepsin L and the turnover of γ-interferon-inducible lysosomal thiol reductase in B lymphocytes. J. Biol. Chem. 276, 22573-22578 (2001).
47. Benavides, F. et al. The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (Ctsl) gene. Immunogenetics 53, 233-242 (2001).
48. Santamaria, I. et al. Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal carcinomas. Cancer Res. 58, 1624-1630 (1998).
49. Bromme, D., Li, Z., Barnes, M. & Mehler, E. Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization. Biochemistry 38, 2377-2385 (1999).
50. + T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. J. Exp. Med. 195, 1349-1358 (2002). The first in vivo evidence that cathepsin L has a direct role in generating peptides that bind MHC class II molecules.
51. Rodriguez, G. M. & Diment, S. Role of cathepsin D in antigen presentation of ovalbumin. J. Immunol. 149, 2894-2898 (1992).
52. van Noort, J. M. & Jacobs, M. J. Cathepsin D, but not cathepsin B, releases T cell stimulatory fragments from lysozyme that are functional in the context of multiple murine class II MHC molecules. Eur. J. Immunol. 24, 2175-2180 (1994).
53. Bennett, K. et al. Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E. Eur. J. Immunol, 22, 1519-1524 (1992).
54. Finley, E. M. & Kornfeld, S. Subcellular localization and targeting of cathepsin E. J. Biol. Chem. 269, 31259-31266 (1994).
55. Driessen, C., Lennon-Dumenil, A. M. & Ploegh, H. L. Individual cathepsins degrade immune complexes internalized by antigen-presenting cells via Fcγ receptors. Eur. J. Immunol. 31, 1592-1601 (2001).
56. Hsieh, C. S., deRoos, P., Honey, K., Beers, C. & Rudensky, A. Y. A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation. J. Immunol. 168, 2618-2625 (2002).
57. Pluger, E. B. et al. Specific role for cathepsin S in the generation of antigenic peptides in vivo. Eur. J. Immunol 32, 467-476 (2002).
58. Manoury, B. et al. An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 396, 695-699 (1998). This paper identifies asparagine endopeptidase as a protease involved in the generation of peptide epitopes.
59. Antoniou, A. N., Blackwood, S. L., Mazzeo, D. & Watts, C. Control of antigen presentation by a single protease cleavage site. Immunity 12, 391-398 (2000).
60. Manoury, B. et al. Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP. Nature Immunol. 3, 169-174 (2002).
61. Hewitt, E. W. et al. Natural processing sites for human cathepsin E and cathepsin D in tetanus toxin: implications for T cell epitope generation. J. Immunol. 159, 4693-4699 (1997).
62. Beck, H. et al. Cathepsin S and an asparagine-specific endoprotease dominate the proteolytic processing of human myelin basic protein in vitro. Eur. J. Immunol. 31, 3726-3736 (2001).
63. Shi, G. P. et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J. Exp. Med. 191, 1177-1186 (2000). This paper indicates that cathepsin F has a role in the late stages of Ii degradation in macrophages.
64. Beers, C., Honey, K., Fink, S., Forbush, K. & Rudensky, A. Differential regulation of cathepsin S and cathepsin L in interferon-γ -treated macrophages. J. Exp. Med. 197, 169-179 (2003).
65. Liuzzo, J. P., Petanceska, S. S., Moscatelli, D. & Devi, L. A. Inflammatory mediators regulate cathepsin S in macrophages and microglia: a role in attenuating heparan sulfate interactions. Mol. Med. 5, 320-333 (1999).
66. Wang, Z. et al. Interferon-γ induction of pulmonary emphysema in the adult murine lung. J. Exp. Med. 192, 1587-1600 (2000).
67. Storm van's Gravesande, K. et al. IFN regulatory factor-1 regulates IFN-γ-dependent cathepsin S expression. J. Immunol. 168, 4488-4494 (2002).
68. Mason, R. W., Gal, S. & Gottesman, M. M. The identification of the major excreted protein (MEP) from a transformed mouse fibroblast cell line as a catalytically active precursor form of cathepsin L. J. Biochem. 248, 449-454 (1987).
69. Rowan, A. D., Mason, P., Mach, L. & Mort, J. S. Rat procathepsin B. Proteolytic processing to the mature form in vitro. J. Biol. Chem. 267, 15993-15999 (1992).
70. Mach, L., Mort, J. S. & Glossl, J. Maturation of human procathepsin B. Proenzyme activation and proteolytic processing of the precursor to the mature proteinase, in vitro, are primarily unimolecular processes. J. Biol. Chem. 269, 13030-13035 (1994).
71. McDonald, J. K. & Emerick, J. M. Purification and characterization of procathepsin L, a self-processing zymogen of guinea pig spermatozoa that acts on a cathepsin D assay substrate. Arch. Biochem. Biophys. 323, 409-422 (1995).
72. Menard, R. et al. Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro. J. Biol. Chem. 273, 4478-4484 (1998).
73. Dahl, S. W. et al. Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Biochemistry 40, 1671-1678 (2001).
74. Barrett, A. J. The cystatins: a diverse superfamily of cysteine peptidase inhibitors. Biomed. Biochim. Acta 45, 1363-1374 (1986).
75. Henskens, Y. M., Veerman, E. C. & Nieuw Amerongen, A. V. Cystatins in health and disease. Biol. Chem. Hoppe Seyler 377, 71-86 (1996).
76. Leonardi, A., Turk, B. & Turk, V. Inhibition of bovine cathepsins L and S by stefins and cystatins. Biol. Chem. Hoppe Seyler 377, 319-321 (1996).
77. Pierre, P. & Mellman, I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 93, 1135-1145 (1998).
78. Villadangos, J. A. et al. MHC class II expression is regulated in dendritic cells independently of invariant chain degradation. Immunity 14, 739-749 (2001).
79. Lautwein, A. et al. Inflammatory stimuli recruit cathepsin activity to late endosomal compartments in human dendritic cells. Eur. J. Immunol. 32, 3348-3357 (2002).
80. Ogrinc, T., Dolenc, I., Ritonja, A. & Turk, V. Purification of the complex of cathepsin L and the MHC class II-associated invariant chain fragment from human kidney. FEBS Lett. 336, 555-559 (1993).
81. Bevec, T., Stoka, V., Pungercic, G., Dolenc, I. & Turk, V. Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L. J. Exp. Med. 183, 1331-1338 (1996).
82. Fineschi, B., Sakaguchi, K., Appella, E. & Miller, J. The proteolytic environment involved in MHC class II-restricted antigen presentation can be modulated by the p41 form of invariant chain. J. Immunol. 157, 3211-3215 (1996).
83. Guncar, G., Pungercic, G., Klemencic, I., Turk, V. & Turk, D. Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. EMBO J. 18, 793-803 (1999).
84. Shachar, I., Elliott, E. A., Chasnoff, B., Grewal, I. S. & Flavell, R. A. Reconstitution of invariant chain function in transgenic mice in vivo by individual p31 and p41 isoforms. Immunity 3, 373-383 (1995).
85. + T cell function in mice lacking the p41 isoform of invariant chain. Immunity 3, 385-396 (1995).
86. Lennon-Dumenil, A. M. et al. The p41 isoform of invariant chain is a chaperone for cathepsin L. EMBO J. 20, 4055-4064 (2001).
87. Fiebiger, E. et al. Invariant chain controls the activity of extracellular cathepsin L. J. Exp. Med. 196, 1263-1269 (2002).
88. Lennon-Dumenil, A. M. et al. Analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation. J. Exp. Med. 196, 529-540 (2002). A new approach to understanding the regulation of lysosomal cysteine-protease activity.
89. Trombetta, E. S., Ebersold, M., Garrett, W., Pypaert, M. & Mellman, I. Activation of lysosomal function during dendritic cell maturation. Science 299, 1400-1403 (2003). This paper shows that endosome acidification is a crucial event in regulating lysosomal cysteine protease activity after dendritic-cell activation.
90. Bendelac, A., Bonneville, M. & Kearney, J. F. Autoreactivity by design: innate B and T lymphocytes. Nature Rev. Immunol. 1, 177-186 (2001).
91. Kronenberg, M. & Gapin, L. The unconventional lifestyle of NKT cells. Nature Rev. Immunol. 2, 557-568 (2002).
92. Moody, D. B. & Porcelli, S. A. Intracellular pathways of CD1 antigen presentation. Nature Rev. Immunol. 3, 11-22 (2003).
93. + thymocytes selected by MHC class I molecules. Science 263, 1774-1778 (1994).
94. + cells. J. Immunol. 164, 2412-2418 (2000).
95. Zeng, Z. et al. Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277, 339-345 (1997).
96. Joyce, S. et al. Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 279, 1541-1544 (1998).
97. Chiu, Y. H. et al. Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J. Exp. Med. 189, 103-110 (1999).
98. Chiu, Y. H. et al. Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d. Nature Immunol. 3, 55-60 (2002).
99. Roberts, T. J. et al. Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells. J. Immunol. 168, 5409-5414 (2002).
100. Sugita, M. et al. Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells. Immunity 16, 697-706 (2002).
101. Briken, V., Jackman, R. M., Dasgupta, S., Hoening, S. & Porcelli, S. A. Intracellular trafficking pathway of newly synthesized CD1b molecules. EMBO J. 21, 825-834 (2002).
102. Kang, S. J. & Cresswell, P. Regulation of intracellular trafficking of human CD1d by association with MHC class II molecules. EMBO J. 21, 1650-1660 (2002).
103. Jayawardena-Wolf, J., Benlagha, K., Chiu, Y. H., Mehr, R. & Bendelac, A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity 15, 897-908 (2001).
104. Ziegler, H. K. & Unanue, E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc. Natl Acad. Sci. USA 79, 175-178 (1982).
105. Shimonkevitz, R., Kappler, J., Marrack, P. & Grey, H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J. Exp. Med. 158, 303-316 (1983).
106. Nowell, J. & Quaranta, V. Chloroquine affects biosynthesis of la molecules by inhibiting dissociation of invariant (γ) chains from αβ dimers in B cells. J. Exp. Med. 162, 1371-1376 (1985).
107. Harding, C. V., Collins, D. S., Slot, J. W., Gauze, H. J. & Unanue, E. R. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Cell 64, 393-401 (1991).
108. Halangk, W. et al. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J. Clin. Invest. 106, 773-781 (2000).
109. Guicciardi, M. E. et al. Cathepsin B contributes to TNF-α-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J. Clin. Invest. 106, 1127-1137 (2000).
110. Saftig, P. et al. Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells. EMBO J. 14, 3599-3608 (1995).
111. Koike, M. et al. Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. J. Neurosci. 20, 6898-6906 (2000).
112. Wang, B. et al. Human cathepsin F. Molecular cloning, functional expression, tissue localization, and enzymatic characterization. J. Biol. Chem. 273, 32000-32008 (1998).
113. Saftig, P. et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc. Natl Acad. Sci. USA 95, 13453-13458 (1998).
114. Gowen, M. et al. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J. Bone Miner. Res. 14, 1654-1663 (1999).
115. Benavides, F. et al. Impaired hair follide morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation. Am. J. Pathol. 161, 693-703 (2002).
116. Stypmann, J. et al. Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Proc. Natl Acad. Sci. USA 99, 6234-6239 (2002).