Towards a systems understanding of MHC class i and MHC class II antigen presentation

Nature Reviews Immunology

Volumn 11, Issue 12, 2011, Pages 823-836

  Neefjes, Jacques ^a   Jongsma, Marlieke L M ^a   Paul, Petra ^a   Bakke, Oddmund ^b  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; GAMMA INTERFERON; HLA A ANTIGEN; HLA B ANTIGEN; HLA C ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PROTEASOME; PROTEIN DISULFIDE ISOMERASE; REACTIVE OXYGEN METABOLITE;

ALLELE; ANTIGEN PRESENTATION; ANTIGEN SPECIFICITY; APOPTOSIS; CYTOSOL; DNA POLYMORPHISM; DNA SPLICING; ENDOPLASMIC RETICULUM; EPITHELIUM CELL; IMMUNOCOMPETENT CELL; OPEN READING FRAME; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW;

ANIMALS; ANTIGEN PRESENTATION; BIOLOGICAL TRANSPORT; DENDRITIC CELLS; ENDOPLASMIC RETICULUM; GENES, MHC CLASS I; GENES, MHC CLASS II; HISTOCOMPATIBILITY ANTIGENS CLASS I; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; MICE; MODELS, IMMUNOLOGICAL; MULTIPROTEIN COMPLEXES; PEPTIDE FRAGMENTS; POLYMORPHISM, GENETIC; PROTEASOME ENDOPEPTIDASE COMPLEX; RNA, SMALL INTERFERING; STRUCTURE-ACTIVITY RELATIONSHIP; SYSTEMS THEORY;

EID: 82255164138     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3084     Document Type: Review

References (158)

1. Vyas, J. M., Van der Veen, A. G. & Ploegh, H. L. The known unknowns of antigen processing and presentation. Nature Rev. Immunol. 8, 607-618 (2008).
2. Kurts, C., Robinson, B. W. & Knolle, P. A. Cross-priming in health and disease. Nature Rev. Immunol. 10, 403-414 (2010).
3. Crotzer, V. L. & Blum, J. S. Autophagy and adaptive immunity. Immunology 131, 9-17 (2010).
4. Horst, D., Verweij, M. C., Davison, A. J., Ressing, M. E. & Wiertz, E. J. Viral evasion of T cell immunity: ancient mechanisms offering new applications. Curr. Opin. Immunol. 23, 96-103 (2011).
5. Hughes, E. A., Hammond, C. & Cresswell, P. Misfolded major histocompatibility complex class I heavy chains are translocated into the cytoplasm and degraded by the proteasome. Proc. Natl Acad. Sci. USA 94, 1896-1901 (1997). (Pubitemid 27113933)
6. Koopmann, J. O. et al. Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Sec61p channel. Immunity 13, 117-127 (2000).
7. Reits, E. A., Vos, J. C., Gromme, M. & Neefjes, J. The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404, 774-778 (2000). (Pubitemid 30212406)
8. Schubert, U. et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770-774 (2000). (Pubitemid 30212405)
9. Li, M. et al. Widespread RNA and DNA sequence differences in the human transcriptome. Science 333, 53-58 (2011).
10. Yewdell, J. W. & Hickman, H. D. New lane in the information highway: alternative reading frame peptides elicit T cells with potent antiretrovirus activity. J. Exp. Med. 204, 2501-2504 (2007). (Pubitemid 350044774)
11. Berglund, P., Finzi, D., Bennink, J. R. & Yewdell, J. W. Viral alteration of cellular translational machinery increases defective ribosomal products. J. Virol. 81, 7220-7229 (2007). (Pubitemid 46986658)
12. Netzer, N. et al. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature 462, 522-526 (2009).
13. Dolan, B. P. et al. Distinct pathways generate peptides from defective ribosomal products for CD8f T cell immunosurveillance. J. Immunol. 186, 2065-2072 (2011).
14. Khan, S. et al. Cutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein. J. Immunol. 167, 4801-4804 (2001). (Pubitemid 33009706)
15. Vigneron, N. et al. An antigenic peptide produced by peptide splicing in the proteasome. Science 304, 587-590 (2004). (Pubitemid 38541917)
16. Hanada, K., Yewdell, J. W. & Yang, J. C. Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 427, 252-256 (2004). (Pubitemid 38112041)
17. Dalet, A. et al. An antigenic peptide produced by reverse splicing and double asparagine deamidation. Proc. Natl Acad. Sci. USA 108, e323-e331 (2011).
18. Neefjes, J. J. & Ploegh, H. L. Allele and locus-specific differences in cell surface expression and the association of HLA class I heavy chain with β2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association. Eur. J. Immunol. 18, 801-810 (1988).
19. Reits, E. A. et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259-1271 (2006). (Pubitemid 43736595)
20. Kulkarni, S. et al. Differential microRNA regulation of HLA-C expression and its association with HIV control. Nature 472, 495-498 (2011).
21. Apcher, S. et al. Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation. Proc. Natl Acad. Sci. USA 108, 11572-11577 (2011).
22. Gu, W. et al. Both treated and untreated tumors are eliminated by short hairpin RNA-based induction of target-specific immune responses. Proc. Natl Acad. Sci. USA 106, 8314-8319 (2009).
23. Ferrara, T. A., Hodge, J. W. & Gulley, J. L. Combining radiation and immunotherapy for synergistic antitumor therapy. Curr. Opin. Mol. Ther. 11, 37-42 (2009).
24. Mester, G., Hoffmann, V. & Stevanovic, S. Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands. Cell. Mol. Life Sci. 68, 1521-1532 (2011).
25. Sauer, R. T. & Baker, T. A. AAA2 proteases: ATP-fueled machines of protein destruction. Annu. Rev. Biochem. 80, 587-612 (2011).
26. Cascio, P., Hilton, C., Kisselev, A. F., Rock, K. L. & Goldberg, A. L. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. EMBO J. 20, 2357-2366 (2001). (Pubitemid 32452853)
27. Sijts, E. J. & Kloetzel, P. M. The role of the proteasome in the generation of MHC class I ligands and immune responses. Cell. Mol. Life Sci. 68, 1491-1502 (2011).
28. Toes, R. E. et al. Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products. J. Exp. Med. 194, 1-12 (2001). (Pubitemid 32660433)
29. Nitta, T. et al. Thymoproteasome shapes immunocompetent repertoire of CD8f T cells. Immunity 32, 29-40 (2010).
30. Seifert, U. et al. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell 142, 613-624 (2010).
31. Reits, E. et al. Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity 18, 97-108 (2003). (Pubitemid 36120691)
32. Wearsch, P. A. & Cresswell, P. The quality control of MHC class I peptide loading. Curr. Opin. Cell Biol. 20, 624-631 (2008).
33. Park, B. et al. Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing. Cell 127, 369-382 (2006). (Pubitemid 44572373)
34. Wearsch, P. A., Peaper, D. R. & Cresswell, P. Essential glycan-dependent interactions optimize MHC class I peptide loading. Proc. Natl Acad. Sci. USA 108, 4950-4955 (2011).
35. Zarling, A. L. et al. Tapasin is a facilitator, not an editor, of class I MHC peptide binding. J. Immunol. 171, 5287-5295 (2003). (Pubitemid 37441282)
36. Parcej, D. & Tampe, R. ABC proteins in antigen translocation and viral inhibition. Nature Chem. Biol. 6, 572-580 (2010).
37. Blanchard, N. et al. Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells. J. Immunol. 184, 3033-3042 (2010).
38. Serwold, T., Gonzalez, F., Kim, J., Jacob, R. & Shastri, N. ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 419, 480-483 (2002).
39. Saveanu, L. et al. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nature Immunol. 6, 689-697 (2005). (Pubitemid 41716742)
40. Saric, T. et al. An IFN-γ-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides. Nature Immunol. 3, 1169-1176 (2002). (Pubitemid 35476828)
41. York, I. A. et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues. Nature Immunol. 3, 1177-1184 (2002). (Pubitemid 35469702)
42. Roelse, J., Gromme, M., Momburg, F., Hammerling, G. & Neefjes, J. Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J. Exp. Med. 180, 1591-1597 (1994). (Pubitemid 24328551)
43. Neijssen, J. et al. Cross-presentation by intercellular peptide transfer through gap junctions. Nature 434, 83-88 (2005). (Pubitemid 40349389)
44. Pang, B. et al. Direct antigen presentation and gap junction mediated cross-presentation during apoptosis. J. Immunol. 183, 1083-1090 (2009).
45. Saccheri, F. et al. Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity. Sci. Transl. Med. 2, 44ra57 (2010).
46. Trowsdale, J. HLA genomics in the third millennium. Curr. Opin. Immunol. 17, 498-504 (2005). (Pubitemid 41207953)
47. Neisig, A., Melief, C. J. & Neefjes, J. Reduced cell surface expression of HLA-C molecules correlates with restricted peptide binding and stable TAP interaction. J. Immunol. 160, 171-179 (1998). (Pubitemid 28116727)
48. Neisig, A., Wubbolts, R., Zang, X., Melief, C. & Neefjes, J. Allele-specific differences in the interaction of MHC class I molecules with transporters associated with antigen processing. J. Immunol. 156, 3196-3206 (1996). (Pubitemid 26123533)
49. Peh, C. A. et al. HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading. Immunity 8, 531-542 (1998). (Pubitemid 28264744)
50. Leslie, A. et al. Additive contribution of HLA class I alleles in the immune control of HIV-1 infection. J. Virol. 84, 9879-9888 (2010).
51. Malik, P., Klimovitsky, P., Deng, L. W., Boyson, J. E. & Strominger, J. L. Uniquely conformed peptide-containing β2-microglobulin-free heavy chains of HLA-B2705 on the cell surface. J. Immunol. 169, 4379-4387 (2002). (Pubitemid 35178212)
52. Herberts, C. A. et al. Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation. J. Immunol. 176, 2697-2701 (2006).
53. Evans, D. M. et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature Genet. 43, 761-767 (2011).
54. Princiotta, M. F. et al. Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18, 343-354 (2003). (Pubitemid 36351514)
55. Yewdell, J. W., Reits, E. & Neefjes, J. Making sense of mass destruction: quantitating MHC class I antigen presentation. Nature Rev. Immunol. 3, 952-961 (2003). (Pubitemid 37521537)
56. Reits, E. A., Vos, J. C., Gromme, M. & Neefjes, J. The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404, 774-778 (2000). (Pubitemid 30212406)
57. Reits, E. et al. A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. Immunity 20, 495-506 (2004). (Pubitemid 38482126)
58. York, I. A., Bhutani, N., Zendzian, S., Goldberg, A. L. & Rock, K. L. Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation. J. Immunol. 177, 1434-1443 (2006). (Pubitemid 44092476)
59. Kloetzel, P. M. Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nature Immunol. 5, 661-669 (2004). (Pubitemid 39023294)
60. Kessler, J. H. et al. Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes. Nature Immunol. 12, 45-53 (2011).
61. Kawahara, M., York, I. A., Hearn, A., Farfan, D. & Rock, K. L. Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo. J. Immunol. 183, 6069-6077 (2009).
62. Saveanu, L., Carroll, O., Hassainya, Y. & van Endert, P. Complexity, contradictions, and conundrums: studying post-proteasomal proteolysis in HLA class I antigen presentation. Immunol. Rev. 207, 42-59 (2005). (Pubitemid 41415007)
63. Lev, A. et al. The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation. Immunity 28, 787-798 (2008). (Pubitemid 351778406)
64. Lev, A. et al. Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action. Proc. Natl Acad. Sci. USA 107, 6964-6969 (2010).
65. Hessa, T. et al. Protein targeting and degradation are coupled for elimination of mislocalized proteins. Nature 475, 394-397 (2011).
66. Tenzer, S. et al. Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding. Cell. Mol. Life Sci. 62, 1025-1037 (2005). (Pubitemid 40655618)
67. Lundegaard, C., Lund, O., Buus, S. & Nielsen, M. Major histocompatibility complex class I binding predictions as a tool in epitope discovery. Immunology 130, 309-318 (2010).
68. Martayan, A. et al. Class I HLA folding and antigen presentation in β2-microglobulin-defective Daudi cells. J. Immunol. 182, 3609-3617 (2009).
69. Gromme, M. et al. Recycling MHC class I molecules and endosomal peptide loading. Proc. Natl Acad. Sci. USA 96, 10326-10331 (1999). (Pubitemid 29422557)
70. Rocca, A. et al. Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic β2-microglobulin. Mol. Immunol. 29, 481-487 (1992).
71. Neefjes, J. J., Smit, L., Gehrmann, M. & Ploegh, H. L. The fate of the three subunits of major histocompatibility complex class I molecules. Eur. J. Immunol. 22, 1609-1614 (1992).
72. Boname, J. M. et al. Efficient internalization of MHC I requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains. Traffic 11, 210-220 (2010).
73. Bartee, E., Mansouri, M., Hovey Nerenberg, B. T., Gouveia, K. & Fruh, K. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J. Virol. 78, 1109-1120 (2004). (Pubitemid 38095821)
74. Howe, C. et al. Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules. EMBO J. 28, 3730-3744 (2009).
75. Fernando, M. M. et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet. 4, e1000024 (2008).
76. Anders, A. K. et al. HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide. Nature Immunol. 12, 54-61 (2011).
77. Denzin, L. K., Fallas, J. L., Prendes, M. & Yi, W. Right place, right time, right peptide: DO keeps DM focused. Immunol. Rev. 207, 279-292 (2005). (Pubitemid 41415024)
78. Romieu-Mourez, R., Francois, M., Boivin, M. N., Stagg, J. & Galipeau, J. Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-γ, TGF-β, and cell density. J. Immunol. 179, 1549-1558 (2007).
79. Geppert, T. D. & Lipsky, P. E. Antigen presentation by interferon-γ-treated endothelial cells and fibroblasts: differential ability to function as antigen-presenting cells despite comparable Ia expression. J. Immunol. 135, 3750-3762 (1985). (Pubitemid 16250344)
80. Bland, P. MHC class II expression by the gut epithelium. Immunol. Today 9, 174-178 (1988).
81. Koretz, K., Leman, J., Brandt, I. & Moller, P. Metachromasia of 3-amino-9-ethylcarbazole (AEC) and its prevention in immunoperoxidase techniques. Histochemistry 86, 471-478 (1987). (Pubitemid 17060273)
82. Mulder, D. J. et al. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis. Am. J. Pathol. 178, 744-753 (2011).
83. Schonefuss, A. et al. Upregulation of cathepsin S in psoriatic keratinocytes. Exp. Dermatol. 19, e80-e88 (2010).
84. Tjernlund, U. M., Scheynius, A., Kabelitz, D. & Klareskog, L. Anti-Ia-reactive cells in mycosis fungoides: a study of skin biopsies, single epidermal cells and circulating T lymphocytes. Acta Derm. Venereol. 61, 291-301 (1981). (Pubitemid 11034404)
85. Choi, N. M., Majumder, P. & Boss, J. M. Regulation of major histocompatibility complex class II genes. Curr. Opin. Immunol. 23, 81-87 (2011).
86. Muhlethaler-Mottet, A., Otten, L. A., Steimle, V. & Mach, B. Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. EMBO J. 16, 2851-2860 (1997). (Pubitemid 27226221)
87. Reith, W., LeibundGut-Landmann, S. & Waldburger, J. M. Regulation of MHC class II gene expression by the class II transactivator. Nature Rev. Immunol. 5, 793-806 (2005). (Pubitemid 41400853)
88. Smith, M. A. et al. Positive regulatory domain I (PRDM1) and IRF8/Pu.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation. J. Biol. Chem. 286, 7893-7904 (2011).
89. Sisk, T. J., Nickerson, K., Kwok, R. P. & Chang, C. H. Phosphorylation of class II transactivator regulates its interaction ability and transactivation function. Int. Immunol. 15, 1195-1205 (2003). (Pubitemid 37220493)
90. Greer, S. F. et al. Serine residues 286, 288, and 293 within the CIITA: a mechanism for down-regulating CIITA activity through phosphorylation. J. Immunol. 173, 376-383 (2004). (Pubitemid 38797363)
91. Bhat, K. P., Truax, A. D. & Greer, S. F. Phosphorylation and ubiquitination of degron proximal residues are essential for class II transactivator (CIITA) transactivation and major histocompatibility class II expression. J. Biol. Chem. 285, 25893-25903 (2010).
92. Greer, S. F., Zika, E., Conti, B., Zhu, X. S. & Ting, J. P. Enhancement of CIITA transcriptional function by ubiquitin. Nature Immunol. 4, 1074-1082 (2003). (Pubitemid 37428035)
93. Paul, P. et al. A genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation. Cell 145, 268-283 (2011).
94. Busch, R., Doebele, R. C., Patil, N. S., Pashine, A. & Mellins, E. D. Accessory molecules for MHC class II peptide loading. Curr. Opin. Immunol. 12, 99-106 (2000). (Pubitemid 30093457)
95. Bertolino, P. & Rabourdin-Combe, C. The MHC class II-associated invariant chain: a molecule with multiple roles in MHC class II biosynthesis and antigen presentation to CD4r T cells. Crit. Rev. Immunol. 16, 359-379 (1996). (Pubitemid 26419109)
96. Landsverk, O. J., Bakke, O. & Gregers, T. F. MHC II and the endocytic pathway: regulation by invariant chain. Scand. J. Immunol. 70, 184-193 (2009).
97. Bodmer, H., Viville, S., Benoist, C. & Mathis, D. Diversity of endogenous epitopes bound to MHC class II molecules limited by invariant chain. Science 263, 1284-1286 (1994). (Pubitemid 24107550)
98. Viville, S. et al. Mice lacking the MHC class II-associated invariant chain. Cell 72, 635-648 (1993). (Pubitemid 23077750)
99. Bikoff, E. K. et al. Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4r T cell selection in mice lacking invariant chain expression. J. Exp. Med. 177, 1699-1712 (1993). (Pubitemid 23146137)
100. Tewari, M. K., Sinnathamby, G., Rajagopal, D. & Eisenlohr, L. C. A cytosolic pathway for MHC class II-restricted antigen processing that is proteasome and TAP dependent. Nature Immunol. 6, 287-294 (2005). (Pubitemid 41724766)
101. Hofmann, M. W. et al. The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains. J. Biol. Chem. 274, 36153-36158 (1999).
102. Dugast, M., Toussaint, H., Dousset, C. & Benaroch, P. AP2 clathrin adaptor complex, but not AP1, controls the access of the major histocompatibility complex (MHC) class II to endosomes. J. Biol. Chem. 280, 19656-19664 (2005). (Pubitemid 41379489)
103. McCormick, P. J., Martina, J. A. & Bonifacino, J. S. Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proc. Natl Acad. Sci. USA 102, 7910-7915 (2005). (Pubitemid 40781037)
104. Santambrogio, L. et al. Involvement of caspase-cleaved and intact adaptor protein 1 complex in endosomal remodeling in maturing dendritic cells. Nature Immunol. 6, 1020-1028 (2005). (Pubitemid 41486187)
105. 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 349, 669-676 (1991). (Pubitemid 21912130)
106. Sanderson, F. et al. Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments. Science 266, 1566-1569 (1994).
107. Kropshofer, H. et al. Editing of the HLA-DR-peptide repertoire by HLA-DM. EMBO J. 15, 6144-6154 (1996). (Pubitemid 26397886)
108. Engering, A. & Pieters, J. Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells. Int. Immunol. 13, 127-134 (2001). (Pubitemid 32123948)
109. Hsing, L. C. & Rudensky, A. Y. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol. Rev. 207, 229-241 (2005). (Pubitemid 41415021)
110. Hartman, I. Z. et al. A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes. Nature Med. 16, 1333-1340 (2010).
111. Raiborg, C. & Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445-452 (2009).
112. Zwart, W. et al. Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape. Immunity 22, 221-233 (2005). (Pubitemid 40255713)
113. ten Broeke, T., van Niel, G., Wauben, M. H., Wubbolts, R. & Stoorvogel, W. Endosomally stored MHC class II does not contribute to antigen presentation by dendritic cells at inflammatory conditions. Traffic 12, 1025-1036 (2011).
114. 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 61, 171-183 (1990).
115. Nordeng, T. W. et al. The cytoplasmic tail of invariant chain regulates endosome fusion and morphology. Mol. Biol. Cell 13, 1846-1856 (2002). (Pubitemid 34651476)
116. Landsverk, O. J., Barois, N., Gregers, T. F. & Bakke, O. Invariant chain increases the half-life of MHC II by delaying endosomal maturation. Immunol. Cell Biol. 89, 619-629 (2011).
117. Strong, B. S. & Unanue, E. R. Presentation of type B peptide-MHC complexes from hen egg white lysozyme by TLR ligands and type I IFNs independent of H2-DM regulation. J. Immunol. 187, 2193-2201 (2011).
118. Trombetta, E. S., Ebersold, M., Garrett, W., Pypaert, M. & Mellman, I. Activation of lysosomal function during dendritic cell maturation. Science 299, 1400-1403 (2003). (Pubitemid 36254654)
119. Rocha, N. et al. Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150Glued and late endosome positioning. J. Cell Biol. 185, 1209-1225 (2009).
120. Kuipers, H. F. et al. Statins affect cell-surface expression of major histocompatibility complex class II molecules by disrupting cholesterol- containing microdomains. Hum. Immunol. 66, 653-665 (2005). (Pubitemid 40922554)
121. Cella, M., Engering, A., Pinet, V., Pieters, J. & Lanzavecchia, A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 388, 782-787 (1997). (Pubitemid 27375158)
122. Pierre, P. et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388, 787-792 (1997). (Pubitemid 27375159)
123. Boes, M. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983-988 (2002). (Pubitemid 34976034)
124. 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). (Pubitemid 26372919)
125. Kleijmeer, M. et al. Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. J. Cell Biol. 155, 53-63 (2001). (Pubitemid 34286207)
126. Vascotto, F. et al. The actin-based motor protein myosin II regulates MHC class II trafficking and BCR-driven antigen presentation. J. Cell Biol. 176, 1007-1019 (2007). (Pubitemid 46506973)
127. Saftig, P. & Klumperman, J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nature Rev. Mol. Cell Biol. 10, 623-635 (2009).
128. de Gassart, A. et al. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proc. Natl Acad. Sci. USA 105, 3491-3496 (2008). (Pubitemid 351723580)
129. Shin, J. S. et al. Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination. Nature 444, 115-118 (2006).
130. Thibodeau, J. et al. Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. Eur. J. Immunol. 38, 1225-1230 (2008).
131. Koppelman, B., Neefjes, J. J., de Vries, J. E. & Waal Malefyt, R. Interleukin-10 down-regulates MHC class II αβ peptide complexes at the plasma membrane of monocytes by affecting arrival and recycling. Immunity 7, 861-871 (1997). (Pubitemid 28064899)
132. Tze, L. E. et al. CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. J. Exp. Med. 208, 149-165 (2011).
133. McGehee, A. M. et al. Ubiquitin-dependent control of class II MHC localization is dispensable for antigen presentation and antibody production. PLoS ONE 6, e18817 (2011).
134. Walseng, E. et al. Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. Proc. Natl Acad. Sci. USA 107, 20465-20470 (2010).
135. Al Daccak, R., Mooney, N. & Charron, D. MHC class II signaling in antigen-presenting cells. Curr. Opin. Immunol. 16, 108-113 (2004). (Pubitemid 38198124)
136. Drenou, B. et al. A caspase-independent pathway of MHC class II antigen-mediated apoptosis of human B lymphocytes. J. Immunol. 163, 4115-4124 (1999). (Pubitemid 29474473)
137. Hemon, P. et al. MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J. Immunol. 186, 5173-5183 (2011).
138. Liu, X. et al. Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nature Immunol. 12, 416-424 (2011).
139. Lang, P. et al. TCR-induced transmembrane signaling by peptide/MHC class II via associated Ig-α/β dimers. Science 291, 1537-1540 (2001). (Pubitemid 32179218)
140. Bonnefoy, J. Y. et al. The low-affinity receptor for IgE (CD23) on B lymphocytes is spatially associated with HLA-DR antigens. J. Exp. Med. 167, 57-72 (1988). (Pubitemid 18093693)
141. Bradbury, L. E., Kansas, G. S., Levy, S., Evans, R. L. & Tedder, T. F. The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J. Immunol. 149, 2841-2850 (1992).
142. van der Burg, S. H. & Melief, C. J. Therapeutic vaccination against human papilloma virus induced malignancies. Curr. Opin. Immunol. 23, 252-257 (2011).
143. Mitea, C. et al. A universal approach to eliminate antigenic properties of α-gliadin peptides in celiac disease. PLoS ONE 5, e15637 (2010).
144. Baugh, M. et al. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J. Autoimmun. 36, 201-209 (2011).
145. Fallang, L. E. et al. Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nature Immunol. 10, 1096-1101 (2009).
146. Chow, K. M. et al. Studies on the subsite specificity of rat nardilysin (N-arginine dibasic convertase). J. Biol. Chem. 275, 19545-19551 (2000). (Pubitemid 30441547)
147. Chow, K. M. et al. Nardilysin cleaves peptides at monobasic sites. Biochemistry 42, 2239-2244 (2003). (Pubitemid 36258698)
148. York, I. A. et al. The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation. Immunity 18, 429-440 (2003). (Pubitemid 36351521)
149. Kim, S. I., Pabon, A., Swanson, T. A. & Glucksman, M. J. Regulation of cell-surface major histocompatibility complex class I expression by the endopeptidase EC3.4.24.15 (thimet oligopeptidase). Biochem. J. 375, 111-120 (2003). (Pubitemid 37255386)
150. Rock, K. L., York, I. A., Saric, T. & Goldberg, A. L. Protein degradation and the generation of MHC class I-presented peptides. Adv. Immunol. 80, 1-70 (2002). (Pubitemid 34625620)
151. Bhutani, N., Venkatraman, P. & Goldberg, A. L. Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation. EMBO J. 26, 1385-1396 (2007). (Pubitemid 46398712)
152. Stoltze, L. et al. Two new proteases in the MHC class I processing pathway. Nature Immunol. 1, 413-418 (2000).
153. Parmentier, N. et al. Production of an antigenic peptide by insulin-degrading enzyme. Nature Immunol. 11, 449-454 (2010).
154. Shen, X. Z., Lukacher, A. E., Billet, S., Williams, I. R. & Bernstein, K. E. Expression of angiotensin-converting enzyme changes major histocompatibility complex class I peptide presentation by modifying C termini of peptide precursors. J. Biol. Chem. 283, 9957-9965 (2008).
155. Chang, S. C., Momburg, F., Bhutani, N. & Goldberg, A. L. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc. Natl Acad. Sci. USA 102, 17107-17112 (2005). (Pubitemid 41692691)
156. Hammer, G. E., Gonzalez, F., James, E., Nolla, H. & Shastri, N. In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nature Immunol. 8, 101-108 (2007). (Pubitemid 46242364)
157. Nguyen, T. T. et al. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nature Struct. Mol. Biol. 18, 604-613 (2011).
158. Kreisel, D. et al. Cutting edge: MHC class II expression by pulmonary nonhematopoietic cells plays a critical role in controlling local inflammatory responses. J. Immunol. 185, 3809-3813 (2010).