Making sense of mass destruction: Quantitating MHC class I antigen presentation

Nature Reviews Immunology

Volumn 3, Issue 12, 2003, Pages 952-961

  Yewdell, Jonathan W ^a   Reits, Eric ^b   Neefjes, Jacques ^b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; AMINOPEPTIDASE; DEFECTIVE RIBOSOMAL PRODUCT PROTEIN; F BOX PROTEIN; HEAT SHOCK PROTEIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PEPTIDE; PEPTONE; PROTEASOME; PROTEIN; PROTEINASE; RIBOSOME PROTEIN; TAPASIN; UNCLASSIFIED DRUG; VIRUS PROTEIN;

AMINO ACID SEQUENCE; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; BLEACHING; CELL DESTRUCTION; COMPLEX FORMATION; CYTOPLASM; ENDOPLASMIC RETICULUM; HUMAN; IMMUNE RESPONSE; MOLECULE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN SYNTHESIS; PROTEIN TRANSPORT; QUANTITATIVE ANALYSIS; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; VIRUS INFECTION;

EID: 0346521283     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1250     Document Type: Review

References (92)

1. Garboczi, D. N. et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384, 134-141 (1996).
2. Garcia, K. C. et al. An αβ T cell receptor structure at 2.5 Å and its orientation in the TCR-MHC complex. Science 274, 209-219 (1996).
3. Falk, K., Rotzschke, O., Stevanovic, S., Jung, G. & Rammensee, H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351, 290-296 (1991).
4. Rock, K. L. et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78, 761-771(1994).
5. Reits, E. A., Benham, A. M., Plougastel, B., Neefles, J. & Trowsdale, J. Dynamics of proteasome distribution in living cells. EMBO. J. 16, 6087-6094 (1997).
6. Kisselev, A. E., Akopian, T. N., Woo, K. M. & Goldberg, A. L. The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation. J. Biol. Chem. 274, 3363-3321 (1999). This paper identifies the peptides that are generated by the proteasome under in vitro conditions. Only a small fraction of all peptides that are released by the proteasomes can bind directly with high affinity to MHC class I molecules. A marked fraction of peptides are too short for transport by transporter for antigen processing (TAP) and binding to MHC class I molecules.
7. 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). This report describes the fate of peptides in living cells. Using bleaching techniques, it is shown that peptides associate with chromatin. However, peptides have to leave the nucleus to contact TAP and are rapidly degraded in the cytoplasm by resident peptidases. As a result, more than 99% will not reach TAP for translocation into the endoplasmic reticulum (ER).
8. 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).
9. Saric, T. et al. IFN-γ-induced aminopeptidase in the ER, ERAP1, trimms precursors to MHC class I-presented peptides. Nature Immunol 3, 1160-1176 (2002).
10. Neefjes, J. J., Momburg, F. & Hammerling, G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science 261, 769-771 (1993).
11. van Endert, P. M., Saveanu, L., Hewitt E. W. & Lehner, P. Powering the peptide pump: TAP crosstalk with energetic nucleotides. Trends Biochem. Sci. 27, 454-461 (2002).
12. Ortmann, B. et al. A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes. Science 277, 1306-1309 (1997).
13. Garbi, N. et al. Impaired immune responses and altered peptide repertoire in tapasin-deficient mice. Nature Immunol. 1, 234-238 (2000).
14. Dick, T. P., Bangia, N., Peaper, D. R. & Cresswell, P. Disulfide bond isomerization and the assembly of MHC class I-peptide complexes. Immunity 16, 87-98 (2002).
15. 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).
16. Momburg, F., Roelse, J., Hammerling, G. J. & Neefjes, J. J. Peptide size selection by the major histocompatibility complex-encoded peptide transporter. J. Exp. Med. 179, 1613-1623 (1994).
17. 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).
18. Zweerink, H. J. et al. Presentation of endogenous peptides to MHC class I-restricted cytotoxic T lymphocytes in transport deletion mutant T2 cells. J. Immunol. 150, 1763-1771 (1993).
19. Wei, M. L. & Cresswell, P. HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides. Nature 356, 443-446 (1992).
20. Williams, D. B., Swiedler, S. J. & Hart, G. W. Intracellular transport of membrane glycoproteins: two closely related histocompatibility antigens differ in their rates of transit to the cell surface. J. Cell Biol. 101, 725-734 (1985).
21. 2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association. Eur. J. Immunol. 18, 801-810 (1988).
22. Lammert, E., Stevanovic, S., Brunner, J., Rammensee, H. G. & Schild, H. Protein disulfide isomerase is the dominant acceptor for peptides translocated into the endoplasmic reticulum. Eur. J. Immunol. 27, 1685-1690 (1997).
23. Spee, P. & Neefjes, J. TAP-translocated peptides specifically bind proteins in the endoplasmic reticulum, including gp96, protein disulfide isomerase and calreticulin. Eur. J. Immunol. 27, 2441-2449 (1997).
24. Koopmann, J. O. et al. Export of antigenic peptides from the endoplasmic reticulum intersects with retrograde protein translocation through the Set61p channel. Immunity 13, 117-127 (2000).
25. Roelse, J., Gromme, M., Momburg, F., Hammerfing, G. & Neefjes, J. Trimming TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J. Exp. Med. 180, 1591-1597 (1994).
26. Seifert, U. et al. An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope. Nature Immunol. 4, 375-379 (2003).
27. Glas, R., Bogyo, M., McMaster, J. S., Gaczynska, M. & Ploegh, H. L. A proteolytic system that compensates for loss of proteasome function. Nature 392, 618-622 (1998).
28. Princiotta, M. F. et al. Cells adapted to the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued suvival. Proc. Natl. Acad. Sci. USA 98, 513-518 (2001).
29. Gromme, M. et al. Recycling MHC class I molecules and endosomal peptide loading. Proc. Natl Acad. Sci. USA 96, 10326-10331 (1999).
30. Kleijmeer, M. J. et al. Antigen loading of MHC class I molecules in the endocytic tract. Traffic 2, 124-137 (2001).
31. Jackson, P. K. et al. The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol. 10, 429-439 (2000).
32. Glickman, M. H. & Ciechanover, A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373-428 (2002).
33. Navon, A. & Goldberg, A. L. Proteins are unfolded on the surface of the ATPase dng before transport into the proteasome. Mol. Cell 8, 1339-1349 (2001).
34. Benaroudj, N., Zwickl, P., Seemuller, E., Baumeister, W. & Goldberg, A. L. ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation. Mol. Cell 11, 69-78 (2003).
35. Ogura, T. & Tanaka, K. Dissecting various ATP-dependent steps involved in proteasomal degradation. Mol. Cell 11, 3-5 (2003).
36. Kloetzel, P. M. Antigen processing by the proteasome. Nature Rev. Mol. Cell Biol. 2, 179-187 (2001).
37. 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). This paper, together with reference 39, provides examples of various peptidases that either generate or destroy peptides for MHC class I antigen presentation. This depends on peptide size and sequence.
38. Stoltze, L. et al. Two new proteases in the MHC class I processing pathway. Nature Immunol. 1, 413-418 (2000).
39. 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).
40. Neisig, A. et al. Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences. J. Immunol. 154, 1273-1279 (1995).
41. De Plaen, E. et al. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum-antigen P91A and identification of the tum-mutation. Proc. Natl Acad. Sci. USA 85, 2274-2278 (1988).
42. Schwab, S. R., Li, K. C., Kang, C. & Shastri, N. Constitutive display of cryptic translation products by MHC class I molecules. Science 301, 1367-1371 (2003).
43. Yewdell, J. W., Anton, L. C. & Bennink, J. R. Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class molecules? J. Immunol. 157, 1823-1826 (1996). The first paper to describe the concept of defective ribosomal products (DRiPs).
44. Bach, I. & Ostendorff, H. P. Orchestrating nuclear functions: ubiquitin sets the rhythm. Trends Biochem. Sci. 28, 189-195 (2003).
45. Jackson, P. K. & Eldridge, A. G. The SCF ubiquitin ligase: an extended look. Mol. Cell 9, 923-925 (2002).
46. Schimke, R. T. & Doyle, D. Control of enzyme levels in animal tissues. Annu. Rev. Biochem. 39, 929-976 (1970).
47. Goldberg, A. Intracellular protein degradation in mammaliann and bacterial cells. Annu. Rev. Biochem. 45, 747-803 (1976).
48. Yewdell, J. W. Not such a dismal science: the economics of protein synthesis, folding, degradation and antigen processing. Trends Cell Biol. 11, 294-297 (2001).
49. Yewdell, J. W., Schubert, U. & Bennink, J. R. At the crossroads of cell biology and Immunology: DRiPs and other sources of peptide ligands for MHC class I molecules. J. Cell Sci. 114, 845-851 (2001).
50. Esquivel, F., Yewdell, J. & Bennink, J. RMA/S cells present endogenously synthesized cytosolic proteins to class I-resticted cytotoxic T lymphocytes. J. Exp. Med. 175, 163-168 (1992).
51. 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). References 51, 52 and 56 provide biochemical, cell biological and immunological evidence for the DRiP hypothesis. They imply that protein generation is tightly linked to antigen presentation by MHC class I molecules.
52. Reits, E. A., Vos, J. C., Gromme, M. & Neefjes. J. The major substrates for TAP in vivo are denved from newly synthesized proteins. Nature 404, 774-778 (2000).
53. Schild, H. & Rammensee, H. G. Perfect use of imperfection. Nature 404, 709-710 (2000).
54. Wheatley, D. N. & Inglis, M. S. Turnover of nascent proteins in HeLa-S3 cells and the quasi-linear incorporation kinetics of amino acids. Cell Biol. Int. Rep. 9, 463-470 (1985).
55. Wheatley, D. N. Protein turnover in relation to growth status and the cell cycle in cultured mammalian cells. Revis. Biol. Cellular 21, 377-400 (1989).
56. Schubert, U. et al. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770-774 (2000).
57. Turner, G. C. & Varshavsky, A. Detecting and measuring cotranslational protein degradation in vivo. Science 289, 2117-2120 (2000).
58. Jensen, T. J. et al. Multiple proteolytic systems, including theproteasome, contribute to CFTR processing. Cell 83, 129-135 (1995).
59. Ward. C. L., Omura, S. & Kopito, R. R. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83, 121-127 (1995).
60. Pareek, S. et al. Neurons promote the translocation of peripheral myelin protein 22 into myelin. J. Neurosci. 17, 7754-7762 (1997).
61. Notterpek. L., Ryan, M. C., Tobler, A. R. & Shooter, E. M. PMP22 accumulation in aggresomes: implications for CMT1A pathology. Neurobiol. Dis. 6, 450-460 (1999).
62. Siffroi-Fernandez, S., Giraud, A., Lanet, J. & Franc, J. L. Association of the thyrotropin receptor with calnexin, calreticulin and BiP. Efects on the maturation of the receptor. Eur. J. Biochem. 269, 4930-4937 (2002)
63. Petaja-Repo, U. E. et al. Newly synthesized human δ-opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome. J. Biol. Chem. 276, 4416-4423 (2001).
64. Yedidia, Y., Horonchik, L., Tzaban, S., Yanai, A. & Taraboulos, A. Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein. EMBO J. 20, 5383-5391 (2001).
65. Drisaldi, B. et al. Mutant PrP is delayed in its exit from the endoplasmic reticulum, but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation. J. Biol. Chem. 278, 21732-21743 (2003).
66. Princiotta, M. F. et al. Quantitating protein synthesis, degradation, and endogenous antigen processing, Immunity 18, 343-354 (2003). This paper shows the full quantification of the steps between protein synthesis and MHC class I antigen presentation. It visualizes the impact of DRiPs on MHC class-I-associated peptides.
67. Kenniston, J. A., Baker, T. A., Fernandez, J. M. & Sauer, R. T Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+ degradation machine. Cell 114, 511-520 (2003).
68. Verma, R. & Deshaies, R. J. A proteasome howdunit: the case of the missing signal. Cell 101, 341-344 (2000).
69. Dantuma, N. P., Lindsten, K., Glas, P., Jellne, M. & Masucci, M. G. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nature Biotechnol. 18, 538-543 (2000).
70. Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552-1555 (2001).
71. Falk, K., Rotzschke, O. & Rammensee, H. G. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348, 248-251 (1990).
72. Porgador, A., Yewdell, J. W., Deng, Y., Bennink, J. R. & Germain, R. N. Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. Immunity 6, 715-726 (1997).
73. Benham, A. M. & Neefjes, J. J. Proteasome activity limits the assembly of MHC class I molecules after IFN-γ stimulation. J. Immunol. 159, 5896-5904 (1997).
74. Anton, L. C. et al. Dissociation of proteasomal degradation of biosynthesized viral proteins from generation of MHC class I-associated antigenic peptides. J. Immunol. 160, 4859-4868 (1998).
75. Ben-Shahar, S. et al. 26 S proteasome-mediated production of an authentic major histocompatibility class I-restricted epitope from an intact protein substrate. J. Biol. Chem. 274, 21963-21972 (1999).
76. Fruci, D. et al. Quantifying recruitment of cytosolic peptides for HLA class I presentation: impact of TAP transport. J. Immunol. 170, 2977-2984 (2003).
77. Villanueva, M. S., Fischer, P., Feen, K. & Pamer, E. G. Efficiency of MHC class I antigen processing: a quantitative analysis. Immunity 1, 479-489 (1994).
78. Guermonprez, P. et al. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425, 397-402 (2003).
79. Houde, M. et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 425, 402-406 (2003).
80. Denkberg, G. et al. Direct visualization of distinct T cell epitopes derived from a melanoma tumor-associated antigen by using human recombinant antibodies with MHC-restricted T cell receptor-like specificity. Proc. Natl. Acad. Sci. USA 99, 9421-9426 (2002).
81. Jardetzky, T. S., Lane, W. S., Robinson, R. A., Madden, D. R. & Wiley, D. C. Identification of self peptides bound to purified HLA-B27. Nature 353, 326-329 (1991).
82. Admon, A., Barnea, E. & Ziv, T. Tumor antigens and proteomics from the point of view of the major histocompatibility complex peptides. Mol. Cell. Proteomics 2, 388-398 (2003).
83. Turzynski, A. & Mentlein, R. Prolyl aminopeptidase from rat brain and kidney. Action on peptides and identification as leucyl aminopeptidase. Eur. J. Biochem. 190, 509-515 (1990).
84. Beninga, J., Rock, K. L. & Goldberg, A. L. lnterferon-γ can stimulate post-proteasomal tdmming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. J. Biol. Chem. 273, 18734-18742 (1998).
85. Geier, E. et al. A giant protease with potential to substitute for some functions of the proteasome. Science 283, 978-981 (1999.)
86. Macpherson, E., Tomkinson, B., Balow, R. M., Hoglund, S. & Zetterqvist, O. Supramolecular structure of tripeptidyl peptidase II from human erythrocytes as studied by electron microscopy, and its correlation to enzyme actvity. Biochem. J. 248, 259-263 (1987).
87. Tomkinson, B. Tripeptidyl peptidases: enzymes that count. Trends Biochem. Sci. 24, 355-359 (1999).
88. Saric, T. et al. Major histocompatiblfity complex class I-presented antigenic peptides are degraded in cytosolic extracts primarily by thimet oligopeptidase. J. Biol Chem. 276, 36474-36481 (2001).
89. Bromme, D., Rossi, A. B., Smeekens, S. P., Anderson, D. C. & Payan, D. G. Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic charactenzation. Biochemistry 35, 6706-6714 (1996).
90. Johnson, G. D. & Hersh, L. B. Studies on the subsite specificity of the rat brain puromycin-sensitive aminopeptidase. Arch. Biochem. Biophys. 276, 305-309 (1990).
91. Gakamsky, D. M., Davis, D. M., Strominger, J. L. & Pecht, I. Assembly and dissociation of human leukocyte antigen (HLA)-A2 studied by real-time fluorescence resonance energy transfer. Biochemistry 39, 11163-11169 (2000).
92. Thulasiraman, V., Yang, C. F. & Frydman, J. In vivo newly translated polypeptides are sequestered in a protected folding environment. EMBO J. 18, 85-95 (1999).