The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking peptide epitope

Journal of Experimental Medicine

Volumn 188, Issue 6, 1998, Pages 1017-1028

  Theobald, Matthias ^a   Ruppert, Thomas ^b   Kuckelkorn, Ulrike ^c   Hernandez, Javier ^d   Häussler, Annett ^a   Ferreira, Edite Antunes ^a   Liewer, Ulrike ^a   Biggs, Judith ^d   Levine, Arnold J ^e   Huber, Christoph ^a   Koszinowski, Ulrich H ^b   Kloetzel, Peter M ^c   Sherman, Linda A ^d  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c HUMBOLDT UNIVERSITY   (Germany)

^d SCRIPPS RESEARCH INSTITUTE   (United States)

^e PRINCETON UNIVERSITY   (United States)

Author keywords

Antigen processing; Cytotoxic T lymphocytes; p53; Proteasomes; Tumor antigens

Indexed keywords

PROTEASOME; PROTEIN P53;

AMINO ACID SEQUENCE; ANIMAL CELL; ANTIGEN PRESENTATION; ARTICLE; CARCINOGENESIS; CYTOTOXIC T LYMPHOCYTE; GENE MUTATION; IMMUNOSURVEILLANCE; MOUSE; NONHUMAN; OSTEOSARCOMA; PRIORITY JOURNAL; TUMOR; TUMOR SUPPRESSOR GENE;

AMINO ACID SEQUENCE; ANIMALS; ANTIGEN PRESENTATION; ARGININE; BINDING SITES; CELL DIVISION; CYSTEINE ENDOPEPTIDASES; CYTOTOXICITY TESTS, IMMUNOLOGIC; CYTOTOXICITY, IMMUNOLOGIC; EPITOPES, T-LYMPHOCYTE; HISTIDINE; HLA-A ANTIGENS; HUMANS; HYDROLYSIS; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; MULTIENZYME COMPLEXES; PEPTIDE FRAGMENTS; PEPTIDES; POINT MUTATION; PROTEASOME ENDOPEPTIDASE COMPLEX; SUBSTRATE SPECIFICITY; T-LYMPHOCYTES, CYTOTOXIC; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53;

EID: 0032555911     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.188.6.1017     Document Type: Article

References (70)

1. Levine, A.J., J. Momand, and C.A. Finlay. 1991. The p53 tumor suppressor gene. Nature. 351:453-456.
2. Hollstein, M., D. Sidransky, B. Vogelstein, and C.C. Harris. 1991. p53 mutations in human cancers. Science. 253:49-53.
3. Denissenko,. M.F., A. Pao, M. Tang, and G.P. Pfeifer. 1996. Preferential formation of benzo[a]pyrene adduces at lung cancer mutational hotspots in p53. Science. 274:430-432.
4. Theobald, M., J. Biggs, D. Dittmer, A.J. Levine, and L.A. Sherman. 1995. Targeting p53 as a general tumor antigen. Proc. Natl. Acad. Sci. USA. 92:11993-11997.
5. Roth, J., D. Dittmer, D. Rea, J. Tartaglia, E. Paoletti, and A.J. Levine. 1996. p53 as a target for cancer vaccines: recombinant canarypox virus vectors expressing p53 protect mice against lethal tumor challenge. Proc. Natl. Acad. Sci. USA. 93: 4781-4786.
6. Röpke, M., J. Hald, P. Guldberg, J. Zeuthen, L. Norgaard, L. Fugger, A. Svejgaard, S. Van Der Burg, H.W. Nijman, C.J.M. Melief, and M.H. Claesson. 1996. Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide. Proc. Natl. Acad. Sci. USA. 93:14704-14707.
7. Mayordomo, J.I., D.J. Loftus, H. Sakamoto, C.M. De Cesare, P.M. Appasamy, M.T. Lotze, W.J. Storkus, E. Appella, and A.B. DeLeo. 1996. Therapy of murine tumors with p53 wild-type and mutant sequence peptide-hased vaccines. J. Exp. Med. 183:1357-1365.
8. Theobald, M., J. Biggs, J. Hernandez, J. Lustgarten, C. Labadie, and L.A. Sherman. 1997. Tolerance to p53 by A2.1-restricted cytotoxic T lymphocytes. J. Exp. Med. 185:833-841.
9. Vierboom, M.P.M., H.W. Nijman, R. Offringa, E.I.H. van der Voort, T. van Hall, L. van den Broek, G.J. Fleuren, P. Kenemans, W.M. Kast, and C.J.M. Melief. 1997. Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. J. Exp. Med. 186:695-704.
10. Houbiers, J.G.A., H.W. Nijman, S.H. van der Burg, J.W. Drijfthout, P. Kenemans, C.J. van de Velde, A. Brand, F. Momburg, W.M. Kast, and C.J.M. Melief. 1993. In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53. Eur. J. Immunol. 23: 2072-2077.
11. Nijman, H.W. J.G.A. Houbiers, S.H. van der Burg, M.P.M. Vierboom, P. Kenemans, W.M. Kast, and C.J.M. Melief. 1993. Characterization of cytotoxic T lymphocyte epitopes of a self-protein, p53, and a non-self-protein, influenza matrix: relationship between major histocompatibility complex peptide binding affinity and immune responsiveness to peptides. J. Immunother. 14:121-126.
12. Nijman, H.W., S.H. van der Burg, M.P.M. Vierboom, J.G.A. Houbiers, W.M. Kast, and C.J.M. Melief. 1994. p53, a potential target for tumor-directed T cells. Immunol. Lett. 40:171-178.
13. Röpke, M., M. Regner, and M.H. Claesson. 1995. T-cell mediated cytotoxicity against p53-protein derived peptides in bulk and limiting dilution cultures of healthy donors. Scand. J. Immunol. 42:98-103.
14. Rock, K.L., C. Gramm, L. Rothstein, K. Clark, R. Stein, L. Dick, D. Hwang, and A.L. Goldberg. 1994. 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.
15. Groettrup, M., A. Soza, U. Kuckelkorn, and P.-M. Kloetzel. 1996. Peptide antigen production by the proteasome: complexity provides efficiency. Immunol. Today. 17:429-435.
16. Lehner, P.J., and P. Cresswell. 1996. Processing and delivery of peptides presented by MHC class I molecules. Curr. Opin. Immunol. 8:59-67.
17. Scheffner, M., B.A. Werness, J.M. Huibregtse, A.J. Levine, and P.M. Howley. 1990. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 63:1129-1136.
18. Maki, C.G., J.M. Huibregtse, and P.M. Howley. 1996. In vivo ubiquitination and proteasome-mediated degradation of p53. Cancer Res. 56:2649-2654.
19. Haupt, Y., R. Maya, A. Kazaz, and M. Oren. 1997. Mdm2 promotes the rapid degradation of p53. Nature. 387:296-299.
20. Kubbutat, M.H., S.N. Jones, and K.H. Vousden. 1997. Regulation of p53 stability by Mdm2. Nature. 387:299-303.
21. Schumacher, T.N., D.V. Kantesaria, M.T. Heemels, P.G. Ashton-Rickardt, J.C. Shepherd, K. Früh, Y. Yang, P.A. Peterson, S. Tonegawa, and H.L. Ploegh. 1994. Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator. J. Exp. Med. 179:533-540.
22. Momburg, F., J. Roelse, G.J. Hämmerling, and J.J. Neefjes. 1994. Peptide size selection by the major histocompatibility complex-encoded peptide transporter. J. Exp. Med. 179: 1613-1623.
23. Van Endert, P.M., R. Tampe, T.H. Meyer, R. Tisch, J.F. Bach, and H.O. McDevitt. 1994. A sequential model for peptide binding and transport by the transporters associated with antigen processing. Immunity. 1:491-500.
24. DeMars, R., R. Rudersdorf, C. Chang, J. Petersen, J. Strandtmann, N. Korn, B. Sidwell, and H.T. Orr. 1985. Mutations that impair a posttranscriptional step in expression of HLA-A and -B antigens. Proc. Natl. Acad. Sci. USA. 82: 8183-8187.
25. Dittmer, D., S. Pati, G. Zambetti, S. Chu, A.K. Teresky, M. Moore, C. Finlay, and A.J. Levine. 1993. Gain of function mutations in p53. Nat. Genet. 4:42-46.
26. Anton, L.C., J.W. Yewdell, and J.R. Bennink. 1997. MHC class I-associated peptides produced from endogenous gene products with vastly different efficiencies. J. Immunol. 158: 2535-2542.
27. Earl, P.L., A.W. Hugin, and B. Moss. 1990. Removal of cryptic poxvirus transcription termination signals from the human immunodeficiency virus type 1 envelope gene enhances expression and immunogenicity ot a recombinant vaccinia virus. J. Virol. 64:2448-2451.
28. Kuckelkorn, U., S. Frentzel, R. Kraft, S. Kostka, M. Groettrup, and P.-M. Kloetzel. 1995. Incorporation of major histocompatibility complex-encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon-γ. Eur. J. Immunol. 25:2605-2611.
29. Dick, T.P., T. Ruppert, M. Groettrup, P.-M. Kloetzel, L. Kuehn, U.H. Koszinowski, S. Stefanovic, H. Schild, and H.-G. Rammensee. 1996. Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands. Cell. 86:253-262.
30. Eggers, M., B. Boes-Fabian, T. Ruppert, P.-M. Kloetzel, and U.H. Koszinowski. 1995. The cleavage preference of the proteasome governs the yield of antigenic peptides. J. Exp. Med. 182:1865-1870.
31. Ossendorp, F., M. Eggers, A. Neisig, T. Ruppert, M. Groettrup, A. Sijts, E. Mengede, P.-M. Kloetzel, J. Neefjes, U. Koszinowski, and C. Melief. 1996. A single residue exchange within a viral CTL epitope alters proteasome-mediated degradation resulting in lack of antigen presentation. Immunity. 5: 115-124.
32. Storkus, W.J., H.J. Zeh III, M.J. Maeurer, R.D. Salter, and M.T. Lotze. 1993. Identification of melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. J. Immunol. 151:3719-3727.
33. + tumor-infiltrating lymphocytes. J. Immunol. 153:1202-1215.
34. Lustgarten, J., M. Theobald, C. Labadie, D. LaFace, P. Peterson, M.L. Disis, M.A. Cheever, and L.A. Sherman. 1997. Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD8. Hum. Immunol. 52:109-118.
35. Sherman, L.A., M. Theobald, D. Morgan, J. Hernandez, I. Bacik, J. Yewdell, J. Bennink, and J. Biggs. 1998. Strategies for tumor elimination by cytotoxic T lymphocytes. Crit. Rev. Immunol. 18:47-54.
36. Shastri, N., T. Serwold, and F. Gonzalez. 1995. Presentation of endogenous peptide/MHC class I complexes is profoundly influenced by specific C-terminal flanking residues. J. Immunol. 155:4339-4346.
37. Roelse, J., M. Gromme, F. Momburg, G. Hämmerling, and J. Neefjes. 1994. Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J. Exp. Med. 180:1591-1597.
38. Snyder, H.L., J.W. Yewdell, and J.R. Bennink. 1994. Trimming of antigenic peptides in an early secretory compartment. J. Exp. Med. 180:2389-2394.
39. Elliott, T., A. Willis, V. Cerundolo, and A. Townsend. 1995. Processing of major histocompatibility class I-restricted antigens in the endoplasmic reticulum. J. Exp. Med. 181:1481-1491.
40. Craiu, A., T. Akopian, A. Goldberg, and K.L. Rock. 1997. Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide. Prof. Natl. Acad. Sci. USA. 94:10850-10855.
41. Boes, B., H. Hengel, T. Ruppert, G. Multhaup, U.H. Koszinowski, and P.-M. Kloetzel. 1994. Interferon γ stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes. J. Exp. Med. 179:901-909.
42. Villanueva, M.S., P. Fischer, K. Feen, and E.G. Pamer. 1994. Efficiency of MHC class I antigen processing: a quantitative analysis. Immunity. 1:479-489.
43. Groettrup, M., T. Ruppert, L. Kuehn, M. Seeger, S. Standera, U. Koszinowski, and P.-M. Kloetzel. 1995. The interferon-gamma-inducible 11S regulator (PA28) and the LMP2/ LMP7 subunits govern the peptide production by the 20S proteasome in vitro. J. Biol. Chem. 270:23808-23815.
44. Niedermann, G., S. Butz, H.G. Ihlenfeldt, R. Grimm, M. Lucchiari, H. Hoschützky, G. Jung, B. Maier, and K. Eichmann. 1995. Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules. Immunity. 2:289-299.
45. Niedermann, G., G. King, S. Butz, U. Birsner, R. Grimm, J. Shabanowitz, D.F. Hunt, and K. Eichmann. 1996. The proteolytic fragments generated by vertebrate proteasomes: structural relationships to major histocompatibility complex class I binding peptide. Proc. Natl. Acad. Sci. USA. 93:8572-8577.
46. Koup, R.A. 1994. Virus escape from CTL recognition. J. Exp. Med. 180:779-782.
47. de Campos-Lima, P.O., V. Levitsky, J. Brooks, S.P. Lee, L.F. Hu, A.B. Rickinson, and M.G. Masucci. 1994. T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues. J. Exp. Med. 179:1297-1305.
48. Goulder, P.J., A.K. Sewell, D.G. Lalloo, D.A. Price, J.A. Whelan, J. Evans, G.P. Taylor, G. Luzzi, P. Giangrande, R.E. Phillips, and A.J. McMichael. 1997. Patterns of immunodominance in HIV-1-specific cytotoxic T lymphocyte responses in two human histocompatibility leukocyte antigens (HLA)-identical siblings with HLA-A(Black star)0201 are influenced by epitope mutation. J. Exp. Med. 185:1423-1433.
49. Moskophidis, D., and R.M. Zinkernagel. 1995. Immunobiology of cytotoxic T-cell escape mutants of lymphocytic choriomeningitis virus. J. Virol. 69:2187-2193.
50. Price, D.A., P.J. Goulder, P. Klenerman, A.K. Sewell, P.J. Easterbrook, M. Troop, C.R. Bangham, and R.E. Phillips. 1997. Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proc. Natl. Acad. Sci. USA. 94:1890-1895.
51. + T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope. J. Exp. Med. 176:1335-1341.
52. Eisenlohr, L.C., J.W. Yewdell, and J.R. Bennink. 1992. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J. Exp. Med. 175:481-487.
53. Del Val, M., H.-J. Schlicht, T. Ruppert, M.J. Reddehase, and U.H. Koszinowski. 1991. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 66: 1145-1153.
54. Bergmann, C.C., L. Tong, R. Cua, J. Sensintaffar, and S. Stohlman. 1994. Differential effects of flanking residues on presentation of epitopes from chimeric peptides. J. Virol. 68: 5306-5310.
55. Bergmann, C.C., Q. Yao, C.-K. Ho, and S.L. Buckwold. 1996. Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes. J. Immunol. 157:3242-3249.
56. Yellen-Shaw, A.J., E.J. Wherry, G.C. Dubois, and L.C. Eisenlohr. 1997. Point mutation flanking a CTL epitope ablates in vitro and in vivo recognition of a full-length viral protein. J. Immunol. 158:3227-3234.
57. Arnold, D., P. Driscoll, M. Androlewicz, E. Hughes, P. Cresswell, and T.A. Spiess. 1992. Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. Nature. 360:171-173.
58. Momburg, F., V. Ortiz-Navarrete, J. Neefjes, E. Goulmy, Y. Vandewal, H. Spits, S.J. Powis, G.W. Butcher, J.C. Howard, P. Walden, and G.J. Hämmerling. 1992. The proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation. Nature. 360:174-177.
59. Driscoll, P., M. Brown, D. Finley, and J.J. Monaco. 1993. MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature. 365:252-264.
60. Gaczynska, M., K.L. Rock, T.A. Spiess, and A.L. Goldberg. 1993. γ-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature. 365:264-267.
61. Gaczynska, M., K.L. Rock, T.A. Spiess, and A.L. Goldberg. 1994. Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP-2 and LMP-7. Proc. Natl. Acad. Sci. USA. 91: 9213-9217.
62. Yewdell, J.W., C. Lapham, I. Bacik, T.A. Spiess, and J.R. Bennink. 1994. MHC-encoded proteasome subunits LMP-2 and LMP-7 are not required for efficient antigen presentation. J. Immunol. 152:1163-1170.
63. Van Kaer, L., P.G. Ashton-Rickardt, M. Eichelberger, M. Gaczynska, K. Nagashima, K.L. Rock, A.L. Goldberg, P.C. Doherty, and S. Tonegawa. 1994. Altered peptidase and viral-specific T cell response in LMP2 mutant mice. Immunity. 1:533-541.
64. Fehling, H.J., W. Swat, C. Laplace, R. Kühn, K. Rajewsky, U. Müller, and H. von Boehmer. 1994. MHC class 1 expression in mice lacking the proteasome subunit LMP-7. Science. 265:1234-1237.
65. Cerundolo, V., A. Kelly, T. Elliott, J. Trowsdale, and A. Townsend. 1995. Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport. Eur. J. Immunol. 25:554-562.
66. Sibille, C., K.G. Gould, K. Willard-Gallo, S. Thomson, A.J. Rivett, S.J. Powis, G.W. Butcher, and P. De Baetselier. 1995. LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes. Curr. Biol. 5: 923-930.
67. Groettrup, M., R. Kraft, S. Kostka, S. Standers, R. Stohwasser, and P.-M. Kloetzel. 1996. A third interferon-γ-induced subunit exchange in the 20S proteasome. Eur. J. Immunol. 26: 863-869.
68. Groettrup, M., S. Standers, R. Stohwasser, and P.M. Kloetzel. 1997. The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome. Proc. Natl. Acad. Sci. USA. 94:8970-8975.
69. Niedermann, G., R. Grimm, E. Geier, M. Maurer, C. Realini, C. Gartmann, J. Soll, S. Omura, M.C. Rechsteiner, W. Baumeister, and K. Eichmann. 1997. Potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system. J. Exp. Med. 185:209-220.
70. Wiedenfeld, E.A., M. Fernandez-Vina, J.A. Berzofsky, and D.P. Carbone. 1994. Evidence for selection against human lung cancers bearing p53 missense mutations which occur within the HLA A(Black star) 0201 peptide consensus motif. Cancer Res. 54:1175-1177.