Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions

Journal of Clinical Investigation

Volumn 102, Issue 6, 1998, Pages 1239-1248

  Sarobe, Pablo ^a,e   Pendleton, C David ^a   Akatsuka, Toshitaka ^b   Lau, Daryl ^c   Engelhard, Victor H ^d   Feinstone, Stephen M ^b   Berzofsky, Jay A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^d UNIVERSITY OF VIRGINIA   (United States)

^e UNIVERSITY OF NAVARRA   (Spain)

Author keywords

Cytotoxic T lymphocyte; Epitope enhancement; Major histocompatibility complex class I affinity; Peptide, synthetic; Vaccine

Indexed keywords

ALANINE; CONCANAVALIN A; CORE PROTEIN; EPITOPE; FREUND ADJUVANT; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HEPATITIS C VACCINE; HLA A2 ANTIGEN; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 6; SYNTHETIC PEPTIDE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIGEN BINDING; ANTIGEN RECOGNITION; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DRUG POTENCY; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; IMMUNOGENICITY; IMMUNOSTIMULATION; NONHUMAN; PRIORITY JOURNAL; SUBCUTANEOUS DRUG ADMINISTRATION; TRANSGENIC MOUSE;

EID: 0032531164     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI3714     Document Type: Article

References (69)

1. Choom, Q.-L., G. Kuo, A.J. Weiner, L.R. Overby, D.W. Bradley, and M. Houghton. 1989. Isolation of a cDNA clone derived from blood-borne non-A, non-B viral hepatitis genome. Science. 244:359-362.
2. Dienstag, J.L. 1983. Non-A, non-B hepatitis. I. Recognition, epidemiology, and clinical features. Gastroenterology. 85:439-462.
3. Townsend, A., and H. Bodmer. 1989. Antigen recognition by class I-restricted T lymphocytes. Annu. Rev. Immunol. 7:601-624.
4. Kast, W.M., R. Offringa, P.J. Peters, A.C. Voordouw, R.H. Meloen, A.J. van der Eb, and C.J.M. Melief. 1989. Eradication of adenovirus E1-induced tumors by E1 A-specific cytotoxic T lymphocytes. Cell. 59:603-614.
5. Kast, W.M., L. Roux, J. Curren, H.J.J. Blom, A.C. Voordouw, R.H. Meloen, D. Kolakofsky, and C.J.M. Melief. 1991. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc. Natl. Acad. Sci. USA. 88:2283-2287.
6. Schulz, M., R.M. Zinkernagel, and H. Hengartner. 1991. Peptide-induced antiviral protection by cytotoxic T cells. Proc. Natl. Acad. Sci. USA. 88:991-993.
7. Taylor, P.M., and B.A. Askonas. 1986. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology. 58:417-420.
8. Shirai, M., H. Okada, M. Nishioka, T. Akatsuka, C. Wychowski, R. Houghten, C.D. Pendleton, S.M. Feinstone, and J.A. Berzofsky. 1994. An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans. J. Virol. 68:3334-3342.
9. Shirai, M., T. Arichi, M. Nishioka, T. Nomura, K. Ikeda, K. Kawanishi, V.H. Engelhard, S.M. Feinstone, and J.A. Berzofsky. 1995. CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1. J. Immunol. 154:2733-2742.
10. Cerny, A., J.G. McHutchison, C. Pasquinelli, M.E. Brown, M.A. Brothers, B. Grabscheid, P. Fowler, M. Houghton, and F.V. Chisari. 1995. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J. Clin. Invest. 95:521-530.
11. Koziel, MJ., D. Dudley, N. Afdhal, Q.-L. Choo, M. Houghton, R. Ralston, and B.D. Walker. 1993. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J. Virol. 67:7522-7532.
12. Battegay, M., J. Fikes, A.M. Di Bisceglie, P.A. Wentworth, A. Sette, E. Celis, W.-M. Ching, A. Grakoui, C.M. Rice, K. Kurokohchi, et al. 1995. Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. J. Virol. 69: 2462-2470.
13. Kita, H., T. Moriyama, T. Kaneko, I. Harase, M. Nomura, H. Miura, I. Nakamura, Y. Yazaki, and M. Imawari. 1993. HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein. Hepatology. 18:1039-1044.
14. Kurokohchi, K., T. Akatsuka, C.D. Pendleton, A. Takamizawa, M. Nishioka, M. Battegay, S.M. Feinstone, and J.A. Berzofsky. 1996. Use of recombinant protein to identify a motif-negative human CTL epitope presented by HLA-A2 in the hepatitis C virus NS3 region. J. Virol. 70:232-240.
15. Koziel, MJ., D. Dudley, J.T. Wong, J. Dienstag, M. Houghton, R. Ralston, and B.D. Walker. 1992. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J. Immunol. 149:3339-3344.
16. Erickson, A.L., M. Houghton, Q.-L. Choo, A.J. Weiner, R. Ralston, E. Muchmore, and C.M. Walker. 1993. Hepatitis C virus-specific responses in the liver of chimpanzees with acute and chronic hepatitis C. J. Immunol. 151:4189-4199.
17. Rehermann, B., K.M. Chang, J.G. McHutchison, R. Kokka, M. Houghton, and F.V. Chisari. 1996. Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. J. Clin. Invest. 98:1432-1440.
18. Chisari, F.V. 1997. Cytotoxic T cells and viral hepatitis. J. Clin. Invest. 99:1472-1477.
19. Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 44:959-968.
20. Germain, R.N., and D.H. Margulies, 1993. The biochemistry and cell biology of antigen processing and presentation. Annu. Rev. Immunol. 11:403-450.
21. Matsumura, M., D.H. Fremont, P.A. Peterson, and I.A. Wilson. 1992. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science. 257:927-934.
22. Falk, K., O. Rötzschke, S. Stevanovic, G. Jung, and H.-G. Rammensee. 1991. Allele-specific motifs revealed by sequencing of self-peptides cluted from MHC molecules. Nature. 351:290-296
23. Hunt, D.F., R.A. Henderson, J. Shahanowitz, K. Sakaguchi, H. Michel, N. Sevilir, A.L. Cox, E. Appella, and V.H. Engelhard. 1992. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science. 255:1261-1263.
24. Kast, W.M., R.M.P. Brandt, J. Sidney, J.-W. Drijfhout, R.T. Kubo, H.M. Grey, C.J.M. Melief, and A. Sette. 1994. Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J. Immunol. 152:3904-3912.
25. Sidney, J., H.M. Grey, S. Southwood, E. Cells, P.A. Wentworth, M.-F. del Guercio, R.T. Kuho, R.W. Chesnut, and A. Sette. 1996. Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-hinding repertoires of common HLA molecules. Hum. Immunol. 45:79-93.
26. Rotzschke, O., and K. Falk. 1991. Naturally-occurring peptide antigens derived from the MHC class-I-restricted processing pathway, Immunol. Today. 12:447-455.
27. Parker, K.C., M.A. Bednarek, L.K. Hull, U. Utz, B. Cunningham, H.J. Zweerink, W.E. Biddison, and J.E. Coligan. 1992. Sequence motifs important for peptide binding to the human MHC class 1 molecule, HLA-A2. J. Immunol. 149:3580-3587.
28. Ruppert, J., J. Sidney, E. Celis, R.T. Kuho, H.M. drey, and A. Sette. 1993. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 74:929-937.
29. Parker, D.C., M.A. Bednarek, and J.E. Coligan. 1994. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J. Immunol. 152:163-175.
30. Wentworth, P.A., A. Sette, E. Celis, J. Sidney, S. Southwood, C. Crimi, S. Stitely, E. Keogh, N.C. Wong, B. Livingston, et al. 1996. Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome. Int. Immunol. 8:651-659.
31. Gulukota, K., and C. DeLisi. 1996. HLA allele selection for designing peplide vaccines. Genet. Anal. 13:81-86.
32. Lipford, G.B., S. Bauer, H. Wagner, and K. Heeg. 1995. Peptide engineering allows cytotoxic T-cell vaccination against human papilloma virus tumour antigen, E6. Immunology. 84:298-303.
33. Lipford, G.B., S. Bauer, H. Wagner, and K. Heeg. 1995. In vivo CTL induction with point-substituted ovalbumin peptides: immunogenicity correlates with peptide-induced MHC class I stability. Vaccine. 13:313-320.
34. Pogue, R.R., J. Eron, J.A. Frelinger, and M. Malsui. 1995. Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicily. Proc. Natl. Acad. Sci. USA. 92:8166-8170.
35. Parkhurst, M.R., M.L. Salgaller, S. Southwood, P.F. Robbins. A. Sette, S.A. Rosenberg, and Y. Kawakami, 1996. Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J. Immunol. 157:2539-2548.
36. Sette, A., A. Vitiello, B. Reherman, P. Fowler, R. Nayersina, W.M. Kast, C.J.M. Melief, C. Oseroff, L. Yuan, J. Ruppert, et al. 1994. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol. 153:5586-5592.
37. Wentworth, P.A., A. Vitiello, J. Sidney, E. Keogh, R.W. Chesnut, H. Grey, and A. Sette. 1996. Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire in humans and human leukocyte and antigen-transgenic mice. Eur. J. Immunol. 26:97-101.
38. Boehncke, W.-H., T. Takeshita, C.D. Pendleton, S. Sadegh-Nasseri, L. Racioppi, R.A. Houghten, J.A. Berzofsky, and R.N. Germain. 1993. The importance of dominant negative effects of amino acids side chain substitution in peptide-MHC molecule interactions and T cell recognition. J. Immunol. 150: 331-341.
39. Alluvia, Y., J.A. Berzofsky, R. Rosenfeld, and H. Margalit. 1994. Sequence features that correlate with MHC restriction. Mol. Immunol. 31:1-19.
40. Mueller, D.L., M.K. Jenkins, and R.H. Schwanz. 1989. Clonal expansion versus functional clonal inaclivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu. Rev. Immunol. 7:445-480.
41. Weaver, C.T., and E.R. Unanue. 1990. The costimulatory function of antigen-presenting cells. Immunol. Today. 11:49-55.
42. Berzofsky, J.A. 1993. Epitope selection and design of synthetic vaccines: molecular approaches to enhancing immunogenicity and cross-reactivity of engineered vaccines. Ann. NY Acad. Sci. 690:256-264.
43. Berzofsky, J.A. 1995. Designing peptide vaccines to broaden recognition and enhance potency. Ann. NY Acad. Sci. 754:161-168.
44. Berzofsky, J.A., and I.J. Berkower. 1995. Novel approaches to peptide and engineered protein vaccines for HIV using defined epitopes: advances in 1994-95. AIDS. 9(Suppl. A):S143-S157.
45. Ahlers, J.D., T. Takeshita, C.D. Pendleton, and J.A. Berzofsky. 1997. Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence. Proc. Natl. Acad. Sci. USA. 94:10856-10861.
46. Paterson, A.C., R. Sciot, M.C. Kew, F. Callea, G.M. Dusheiko, and V.J. Desmet. 1988. HLA expression in human hepatocellular carcinoma. Br. J. Cancer. 57:369-373.
47. Vitiello, A., D. Marchesini, J. Furze, L.A. Sherman, and R.W. Chesnut. 1991. Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex. J. Exp. Med. 173:1007-1015.
48. Newberg, M.H., D.H. Smith, D.R. Vining, E. Lacy, and V.H. Engelhard. 1996. Importance of MHC class 1 α2 and α3 domains in the recognition of self and non-self MHC molecules. J. Immunol. 156:2473-2480.
49. Man, S., M.H. Newberg, V.L. Crotzer, C.J. Luckey, N.S. Williams, Y. Chen, E.L. Huczko, J.P. Ridge, and V.H. Engelhard. 1995. Definition of a human T cell epitope from influenza A non-struetural protein 1 using HLA-A2.1 transgenic mice. Int. Immunol. 7:597-605.
50. Salter, R.D., D.N. Howell, and P. Cresswell. 1985. Genes regulating HLA class I anligen expression in T-B lymphoblasl hybrids. Immunogenetics. 21:235-246.
51. Spies, T., and R. DeMars. 1991. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 351:323-324.
52. Irwin, MJ., W.R. Heath, and L.A. Sherman. 1989. Species-restricted interactions between CD8 and the α3 domain of class I influence the magnitude of the xenogeneic response. J. Exp. Med. 170:1091-1101.
53. Nijman, H.W., J.G.A. Houbiers, M.P.M. Vierboom, S.H. van der Burg, J.W. Drijfhout, J. D'Amaro, P. Kenemans, C.J.M. Melief, and W.M. Kast. 1993. Identification of peptide sequences that potentially trigger HLA-A2.1-restricted cytotoxic T lymphocytes. Eur. J. Immunol. 23:1215-1219.
54. Ahlers, J.D., N. Dunlop, D.W. Ailing, P.L. Nara, and J.A. Berzofsky. 1997. Cytokine-in-adjuvanl steering of the immune response phenotype to HIV-I vaccine constructs: GM-CSF and TNFα synergize with IL-12 to enhance induction of CTL. J. Immunol. 158:3947-3958.
55. Cerny, A., P. Fowler, M.A. Brothers, M. Houghton, H.J. Schlicht, and F.V. Chisari. 1995. Induction in vitro of a primary human antiviral cytotoxic T cell response. Eur. J. Immunol. 25:627-630.
56. Okamoto, H., S. Okada, Y. Sugiyama, K. Kurai, H. lizuka, A. Machida, Y. Miyakawa, and M. Mayumi. 1991. Nucleotide sequence of the genomic RNA of hepatitis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions. J. Gen. Virol. 72:2697-2704.
57. Okamoto, H., K. Kurai, S.-I. Okada, K. Yamamoto, H. Lizuka, T. Tanaka, S. Fukuda, F. Tsuda, and S. Mishiro. 1992. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology. 188:331-341.
58. Ressing, M.E., A. Sette, R.M.P. Brandt, J. Ruppert, P.A. Wentworth, M. Hartman, C. Oseroff, H.M. Grey, C.J.M. Melief, and W.M. Kast. 1995. Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. J. Immunol. 154:5934-5943.
59. Engelhard, V.H., E. Lacy, and J.P. Ridge. 1991. Influenza A-specific, HLA-A2.1-restricted cytotoxic T lymphocytes from HLA-A2.1 transgenic mice recognize fragments of the M1 protein. J. Immunol. 146:1226-1232.
60. Newberg, M.H., J.P. Ridge, D.R. Vining, R.D. Sailer, and V.H. Engelhard. 1992. Species specificity in the interaction of CD8 with the a3 domain of MHC class I molecules. J. Immunol. 149:136-142.
61. Alexander-Miller, M.A., G.R. Leggatt, and J.A. Berzofsky. 1996. Selective expansion of high or low avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc. Natl. Acad. Sci. USA. 93:4102-4107.
62. Gallimore, A., T. Dumrese, H. Hengartne, R.M. Zinkernagel, and H.G. Rammensee. 1998. Protective immunity does not correlate with the hierarchy of virus-specific cytotoxic T cell responses to naturally processed peptides. J. Exp. Med. 187:1647-1657.
63. Takahashi, H., Y. Nakagawa, C.D. Pendleton, R.A. Houghten, K. Yokomuro, R.N. Germain, and J.A. Berzofsky. 1992. Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-I envelope determinant. Science. 255:333-336.
64. d-restricted cytotoxic T lymphocytes. J. Exp. Med. 173:849-858.
65. Simmonds, P., E.C. Holmes, T.-A. Cha, S.-W. Chan, F. McOmish, B. Irvine, E. Beall, P.L. Yap, J. Kolberg, and M.S. Urdea. 1993. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J. Gen. Virol. 74:2391-2399.
66. Ogata, N., H.J. Alter. R.H. Miller, and R.H. Purcell. 1991. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc. Natl. Acad. Sci. USA. 88:3392-3396.
67. Kato, N., M. Hijikata. Y. Ootsuyama, M. Nakagawa, S. Ohkoshi, T. Sugimura, and K. Shimotohno. 1990. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc. Natl Acad. Sci. USA. 87:9524-9528.
68. Sakamoto, M., Y. Akahane, F. Tsuda, T. Tanaka, D.O. Woodfield, and H. Okamoto. 1994. Entire nucleotide sequence and characterization of a hepatitis C virus genotype V/3a. J. Gen. Virol. 75:1761-1768.
69. Vitiello, A., G. Ishioka, H.M. Grey, R. Rose, P. Farness, R. LaFond, L. Yuan, F.V. Chisari, J. Furze, R. Bartholomeuz, et al. 1995. Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. J. Clin. Invest. 95: 341-349.