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*
Wisconsin Regional Primate Research Center and
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715;
Eppimune, San Diego, CA 92121;
§
Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772; and
¶
Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, MA 02129;
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Laboratory of Genetics, University of Wisconsin, Madison, WI 53706
The majority of immunogenic CTL epitopes bind to MHC class I molecules with high affinity. However, peptides longer or shorter than the optimal epitope rarely bind with high affinity. Therefore, identification of optimal CTL epitopes from pathogens may ultimately be critical for inducing strong CTL responses and developing epitope-based vaccines. The SIV-infected rhesus macaque is an excellent animal model for HIV infection of humans. Although a number of CTL epitopes have been mapped in SIV-infected rhesus macaques, the optimal epitopes have not been well defined, and their anchor residues are unknown. We have now defined the optimal SIV gag CTL epitope restricted by the rhesus MHC class I molecule Mamu-A*01 and defined a general peptide binding motif for this molecule that is characterized by a dominant position 3 anchor (proline). We used peptide elution and sequencing, peptide binding assays, and bulk and clonal CTL assays to demonstrate that the optimal Mamu-A*01-restricted SIV gag CTL epitope was CTPYDINQM181–189. Mamu-A*01 is unique in that it is found at a high frequency in rhesus macaques, and all SIV-infected Mamu-A*01-positive rhesus macaques studied to date develop an immunodominant gag-specific CTL response restricted by this molecule. Identification of the optimal SIV gag CTL epitope will be critical for a variety of studies designed to induce CD8+ CTL responses specific for SIV in the rhesus macaque.
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Z. Hel, W.-P. Tsai, A. Thornton, J. Nacsa, L. Giuliani, E. Tryniszewska, M. Poudyal, D. Venzon, X. Wang, J. Altman, et al. Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen J. Immunol., December 15, 2001; 167(12): 7180 - 7191. [Abstract] [Full Text] [PDF]
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S. Sharpe, N. Polyanskaya, M. Dennis, G. Sutter, T. Hanke, V. Erfle, V. Hirsch, and M. Cranage Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques by vaccination with modified vaccinia virus Ankara expressing SIV transgenes: influence of pre-existing anti-vector immunity J. Gen. Virol., September 1, 2001; 82(9): 2215 - 2223. [Abstract] [Full Text] [PDF]
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D. H. Barouch, S. Santra, M. J. Kuroda, J. E. Schmitz, R. Plishka, A. Buckler-White, A. E. Gaitan, R. Zin, J.-H. Nam, L. S. Wyatt, et al. Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination J. Virol., June 1, 2001; 75(11): 5151 - 5158. [Abstract] [Full Text]
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M. Rosenzweig, M. Connole, R. Glickman, S.-P. S. Yue, B. Noren, M. DeMaria, and R. P. Johnson Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34+ hematopoietic cells Blood, April 1, 2001; 97(7): 1951 - 1959. [Abstract] [Full Text] [PDF]
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Y. Xiong, M. A. Luscher, J. D. Altman, M. Hulsey, H. L. Robinson, M. Ostrowski, B. H. Barber, and K. S. MacDonald Simian Immunodeficiency Virus (SIV) Infection of a Rhesus Macaque Induces SIV-Specific CD8+ T Cells with a Defect in Effector Function That Is Reversible on Extended Interleukin-2 Incubation J. Virol., March 15, 2001; 75(6): 3028 - 3033. [Abstract] [Full Text]
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T. U. Vogel, T. M. Allen, J. D. Altman, and D. I. Watkins Functional Impairment of Simian Immunodeficiency Virus-Specific CD8+ T Cells during the Chronic Phase of Infection J. Virol., March 1, 2001; 75(5): 2458 - 2461. [Abstract] [Full Text]
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D. H. Barouch, A. Craiu, S. Santra, M. A. Egan, J. E. Schmitz, M. J. Kuroda, T.-M. Fu, J.-H. Nam, L. S. Wyatt, M. A. Lifton, et al. Elicitation of High-Frequency Cytotoxic T-Lymphocyte Responses against both Dominant and Subdominant Simian-Human Immunodeficiency Virus Epitopes by DNA Vaccination of Rhesus Monkeys J. Virol., March 1, 2001; 75(5): 2462 - 2467. [Abstract] [Full Text]
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J. A. Urvater, H. Hickman, J. L. Dzuris, K. Prilliman, T. M. Allen, K. J. Schwartz, D. Lorentzen, C. Shufflebotham, E. J. Collins, D. L. Neiffer, et al. Gorillas with Spondyloarthropathies Express an MHC Class I Molecule with Only Limited Sequence Similarity to HLA-B27 that Binds Peptides with Arginine at P2 J. Immunol., March 1, 2001; 166(5): 3334 - 3344. [Abstract] [Full Text] [PDF]
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T. M. Allen, B. R. Mothé, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, et al. CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing J. Virol., January 15, 2001; 75(2): 738 - 749. [Abstract] [Full Text]
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T.-M. Fu, D. C. Freed, W. L. Trigona, L. Guan, L. Zhu, R. Long, N. V. Persaud, K. Manson, S. Dubey, and J. W. Shiver Evaluation of Cytotoxic T-Lymphocyte Responses in Human and Nonhuman Primate Subjects Infected with Human Immunodeficiency Virus Type 1 or Simian/Human Immunodeficiency Virus J. Virol., January 1, 2001; 75(1): 73 - 82. [Abstract] [Full Text]
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J. Sidney, J. L. Dzuris, M. J. Newman, R. P. Johnson, K. Amitinder, C. M. Walker, E. Appella, B. Mothe, D. I. Watkins, and A. Sette Definition of the Mamu A*01 Peptide Binding Specificity: Application to the Identification of Wild-Type and Optimized Ligands from Simian Immunodeficiency Virus Regulatory Proteins J. Immunol., December 1, 2000; 165(11): 6387 - 6399. [Abstract] [Full Text] [PDF]
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 D. H. Barouch, S. Santra, J. E. Schmitz, M. J. Kuroda, T.-M. Fu, W. Wagner, M. Bilska, A. Craiu, X. X. Zheng, G. R. Krivulka, et al. Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination Science, October 20, 2000; 290(5491): 486 - 492. [Abstract] [Full Text]
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M. A. Cromwell, R. S. Veazey, J. D. Altman, K. G. Mansfield, R. Glickman, T. M. Allen, D. I. Watkins, A. A. Lackner, and R. P. Johnson Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus J. Virol., September 15, 2000; 74(18): 8762 - 8766. [Abstract] [Full Text]
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D. T. Evans, P. Jing, T. M. Allen, D. H. O'Connor, H. Horton, J. E. Venham, M. Piekarczyk, J. Dzuris, M. Dykhuzen, J. Mitchen, et al. Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression J. Virol., August 15, 2000; 74(16): 7400 - 7410. [Abstract] [Full Text]
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M. A. Egan, W. A. Charini, M. J. Kuroda, J. E. Schmitz, P. Racz, K. Tenner-Racz, K. Manson, M. Wyand, M. A. Lifton, C. E. Nickerson, et al. Simian Immunodeficiency Virus (SIV) gag DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection J. Virol., August 15, 2000; 74(16): 7485 - 7495. [Abstract] [Full Text]
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M. J. Kuroda, J. E. Schmitz, A. Seth, R. S. Veazey, C. E. Nickerson, M. A. Lifton, P. J. Dailey, M. A. Forman, P. Racz, K. Tenner-Racz, et al. Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys Blood, August 15, 2000; 96(4): 1474 - 1479. [Abstract] [Full Text] [PDF]
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P. J. R. Goulder, C. Brander, K. Annamalai, N. Mngqundaniso, U. Govender, Y. Tang, S. He, K. E. Hartman, C. A. O'Callaghan, G. S. Ogg, et al. Differential Narrow Focusing of Immunodominant Human Immunodeficiency Virus Gag-Specific Cytotoxic T-Lymphocyte Responses in Infected African and Caucasoid Adults and Children J. Virol., June 15, 2000; 74(12): 5679 - 5690. [Abstract] [Full Text]
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Z. W. Chen, A. Craiu, L. Shen, M. J. Kuroda, U. C. Iroku, D. I. Watkins, G. Voss, and N. L. Letvin Simian Immunodeficiency Virus Evades a Dominant Epitope-Specific Cytotoxic T Lymphocyte Response Through a Mutation Resulting in the Accelerated Dissociation of Viral Peptide and MHC Class I J. Immunol., June 15, 2000; 164(12): 6474 - 6479. [Abstract] [Full Text] [PDF]
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P. J. R. Goulder, Y. Tang, S. I. Pelton, and B. D. Walker HLA-B57-Restricted Cytotoxic T-Lymphocyte Activity in a Single Infected Subject toward Two Optimal Epitopes, One of Which Is Entirely Contained within the Other J. Virol., June 1, 2000; 74(11): 5291 - 5299. [Abstract] [Full Text]
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T. M. Allen, T. U. Vogel, D. H. Fuller, B. R. Mothe, S. Steffen, J. E. Boyson, T. Shipley, J. Fuller, T. Hanke, A. Sette, et al. Induction of AIDS Virus-Specific CTL Activity in Fresh, Unstimulated Peripheral Blood Lymphocytes from Rhesus Macaques Vaccinated with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen J. Immunol., May 1, 2000; 164(9): 4968 - 4978. [Abstract] [Full Text] [PDF]
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J. L. Dzuris, J. Sidney, E. Appella, R. W. Chesnut, D. I. Watkins, and A. Sette Conserved MHC Class I Peptide Binding Motif Between Humans and Rhesus Macaques J. Immunol., January 1, 2000; 164(1): 283 - 291. [Abstract] [Full Text] [PDF]
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M. Furchner, A. L. Erickson, T. Allen, D. I. Watkins, A. Sette, P. R. Johnson, and C. M. Walker The Simian Immunodeficiency Virus Envelope Glycoprotein Contains Two Epitopes Presented by the Mamu-A*01 Class I Molecule J. Virol., October 1, 1999; 73(10): 8035 - 8039. [Abstract] [Full Text] [PDF]
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N. W. Blake, A. Moghaddam, P. Rao, A. Kaur, R. Glickman, Y.-g. Cho, A. Marchini, T. Haigh, R. P. Johnson, A. B. Rickinson, et al. Inhibition of Antigen Presentation by the Glycine/Alanine Repeat Domain Is Not Conserved in Simian Homologues of Epstein-Barr Virus Nuclear Antigen 1 J. Virol., September 1, 1999; 73(9): 7381 - 7389. [Abstract] [Full Text]
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T. Hanke, R. V. Samuel, T. J. Blanchard, V. C. Neumann, T. M. Allen, J. E. Boyson, S. A. Sharpe, N. Cook, G. L. Smith, D. I. Watkins, et al. Effective Induction of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Macaques by Using a Multiepitope Gene and DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccination Regimen J. Virol., September 1, 1999; 73(9): 7524 - 7532. [Abstract] [Full Text]
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M. A. Egan, M. J. Kuroda, G. Voss, J. E. Schmitz, W. A. Charini, C. I. Lord, M. A. Forman, and N. L. Letvin Use of Major Histocompatibility Complex Class I/Peptide/beta 2M Tetramers To Quantitate CD8+ Cytotoxic T Lymphocytes Specific for Dominant and Nondominant Viral Epitopes in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys J. Virol., July 1, 1999; 73(7): 5466 - 5472. [Abstract] [Full Text]
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H. L. Jordan, M. J. Kuroda, J. E. Schmitz, T. Steenbeke, M. A. Forman, and N. L. Letvin Detection of Simian Immunodeficiency Virus Gag-Specific CD8+ T Lymphocytes in Semen of Chronically Infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I-Peptide Complex J. Virol., May 1, 1999; 73(5): 4508 - 4512. [Abstract] [Full Text]
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M. J. Kuroda, J. E. Schmitz, W. A. Charini, C. E. Nickerson, M. A. Lifton, C. I. Lord, M. A. Forman, and N. L. Letvin Emergence of CTL Coincides with Clearance of Virus During Primary Simian Immunodeficiency Virus Infection in Rhesus Monkeys J. Immunol., May 1, 1999; 162(9): 5127 - 5133. [Abstract] [Full Text] [PDF]
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M. J. Kuroda, J. E. Schmitz, W. A. Charini, C. E. Nickerson, C. I. Lord, M. A. Forman, and N. L. Letvin Comparative Analysis of Cytotoxic T Lymphocytes in Lymph Nodes and Peripheral Blood of Simian Immunodeficiency Virus-Infected Rhesus Monkeys J. Virol., February 1, 1999; 73(2): 1573 - 1579. [Abstract] [Full Text]
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A. Seth, I. Ourmanov, M. J. Kuroda, J. E. Schmitz, M. W. Carroll, L. S. Wyatt, B. Moss, M. A. Forman, V. M. Hirsch, and N. L. Letvin Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer PNAS, August 18, 1998; 95(17): 10112 - 10116. [Abstract] [Full Text] [PDF]
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D. H. Barouch, A. Craiu, M. J. Kuroda, J. E. Schmitz, X. X. Zheng, S. Santra, J. D. Frost, G. R. Krivulka, M. A. Lifton, C. L. Crabbs, et al. Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys PNAS, April 11, 2000; 97(8): 4192 - 4197. [Abstract] [Full Text] [PDF]
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