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. 1992 May;66(5):2928–2933. doi: 10.1128/jvi.66.5.2928-2933.1992

Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells.

M Kannagi 1, H Shida 1, H Igarashi 1, K Kuruma 1, H Murai 1, Y Aono 1, I Maruyama 1, M Osame 1, T Hattori 1, H Inoko 1, et al.
PMCID: PMC241051  PMID: 1373197

Abstract

A trans-acting regulatory gene product p40tax (Tax) of human T-cell leukemia virus type I (HTLV-I) is one of the main target antigens recognized by cytotoxic T lymphocytes (CTL) specific for HTLV-I. A CTL epitope within the Tax protein was identified in this report. HTLV-I-specific CD8+ CTL lines established from two HTLV-I carriers with HTLV-I-associated myelopathy or Sjögren syndrome were previously demonstrated to kill predominantly the target cells expressing HTLV-I Tax. The CTL from two patients showed significant levels of cytotoxicity to autologous target cells pulsed with a synthetic peptide of 24 amino acids corresponding to the amino-terminal sequences of the Tax protein. Allogeneic target cells were also sensitized for CTL by this peptide when the target cells have HLA-A2. Tax-specific cytotoxicity, detected as cytolysis of the target cells infected with vaccinia virus-HTLV-I recombinant expressing Tax protein, was almost completely inhibited by competitor cells pulsed with the synthetic peptide. This indicates that a major CTL epitope is present in this peptide. Further analysis using shorter peptides revealed that the core sequence of the CTL epitope was LLFGYPVYV at positions 11 through 19. This sequence can be aligned with the HLA-A2-specific motifs reported recently.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akizuki S., Nakazato O., Higuchi Y., Tanabe K., Setoguchi M., Yoshida S., Miyazaki Y., Yamamoto S., Sudou S., Sannomiya K. Necropsy findings in HTLV-I associated myelopathy. Lancet. 1987 Jan 17;1(8525):156–157. doi: 10.1016/s0140-6736(87)91984-2. [DOI] [PubMed] [Google Scholar]
  2. Baenziger J., Hengartner H., Zinkernagel R. M., Cole G. A. Induction or prevention of immunopathological disease by cloned cytotoxic T cell lines specific for lymphocytic choriomeningitis virus. Eur J Immunol. 1986 Apr;16(4):387–393. doi: 10.1002/eji.1830160413. [DOI] [PubMed] [Google Scholar]
  3. Cole G. A., Nathanson N., Prendergast R. A. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 1972 Aug 11;238(5363):335–337. doi: 10.1038/238335a0. [DOI] [PubMed] [Google Scholar]
  4. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  5. Garrett T. P., Saper M. A., Bjorkman P. J., Strominger J. L., Wiley D. C. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature. 1989 Dec 7;342(6250):692–696. doi: 10.1038/342692a0. [DOI] [PubMed] [Google Scholar]
  6. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  7. Gessain A., Louie A., Gout O., Gallo R. C., Franchini G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy. J Virol. 1991 Mar;65(3):1628–1633. doi: 10.1128/jvi.65.3.1628-1633.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gessain A., Saal F., Gout O., Daniel M. T., Flandrin G., de The G., Peries J., Sigaux F. High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis. Blood. 1990 Jan 15;75(2):428–433. [PubMed] [Google Scholar]
  9. Green J. E., Hinrichs S. H., Vogel J., Jay G. Exocrinopathy resembling Sjögren's syndrome in HTLV-1 tax transgenic mice. Nature. 1989 Sep 7;341(6237):72–74. doi: 10.1038/341072a0. [DOI] [PubMed] [Google Scholar]
  10. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Itoyama Y., Minato S., Kira J., Goto I., Sato H., Okochi K., Yamamoto N. Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. Neurology. 1988 Aug;38(8):1302–1307. doi: 10.1212/wnl.38.8.1302. [DOI] [PubMed] [Google Scholar]
  13. Iwakura Y., Tosu M., Yoshida E., Takiguchi M., Sato K., Kitajima I., Nishioka K., Yamamoto K., Takeda T., Hatanaka M. Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I. Science. 1991 Aug 30;253(5023):1026–1028. doi: 10.1126/science.1887217. [DOI] [PubMed] [Google Scholar]
  14. Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245–248. doi: 10.1038/348245a0. [DOI] [PubMed] [Google Scholar]
  15. Kannagi M., Harada S., Maruyama I., Inoko H., Igarashi H., Kuwashima G., Sato S., Morita M., Kidokoro M., Sugimoto M. Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. Int Immunol. 1991 Aug;3(8):761–767. doi: 10.1093/intimm/3.8.761. [DOI] [PubMed] [Google Scholar]
  16. Kannagi M., Sugamura K., Kinoshita K., Uchino H., Hinuma Y. Specific cytolysis of fresh tumor cells by an autologous killer T cell line derived from an adult T cell leukemia/lymphoma patient. J Immunol. 1984 Aug;133(2):1037–1041. [PubMed] [Google Scholar]
  17. Kannagi M., Sugamura K., Sato H., Okochi K., Uchino H., Hinuma Y. Establishment of human cytotoxic T cell lines specific for human adult T cell leukemia virus-bearing cells. J Immunol. 1983 Jun;130(6):2942–2946. [PubMed] [Google Scholar]
  18. Nishioka K., Maruyama I., Sato K., Kitajima I., Nakajima Y., Osame M. Chronic inflammatory arthropathy associated with HTLV-I. Lancet. 1989 Feb 25;1(8635):441–441. doi: 10.1016/s0140-6736(89)90038-x. [DOI] [PubMed] [Google Scholar]
  19. Osame M., Usuku K., Izumo S., Ijichi N., Amitani H., Igata A., Matsumoto M., Tara M. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  20. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seiki M., Hikikoshi A., Taniguchi T., Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family. Science. 1985 Jun 28;228(4707):1532–1534. doi: 10.1126/science.2990031. [DOI] [PubMed] [Google Scholar]
  22. Siekevitz M., Feinberg M. B., Holbrook N., Wong-Staal F., Greene W. C. Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5389–5393. doi: 10.1073/pnas.84.15.5389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Siomi H., Shida H., Nam S. H., Nosaka T., Maki M., Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. doi: 10.1016/0092-8674(88)90043-8. [DOI] [PubMed] [Google Scholar]
  24. Sugimoto M., Nakashima H., Watanabe S., Uyama E., Tanaka F., Ando M., Araki S., Kawasaki S. T-lymphocyte alveolitis in HTLV-I-associated myelopathy. Lancet. 1987 Nov 21;2(8569):1220–1220. doi: 10.1016/s0140-6736(87)91362-6. [DOI] [PubMed] [Google Scholar]
  25. Usuku K., Sonoda S., Osame M., Yashiki S., Takahashi K., Matsumoto M., Sawada T., Tsuji K., Tara M., Igata A. HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma. Ann Neurol. 1988;23 (Suppl):S143–S150. doi: 10.1002/ana.410230733. [DOI] [PubMed] [Google Scholar]
  26. Vernant J. C., Buisson G., Magdeleine J., De Thore J., Jouannelle A., Neisson-Vernant C., Monplaisir N. T-lymphocyte alveolitis, tropical spastic paresis, and Sjögren syndrome. Lancet. 1988 Jan 23;1(8578):177–177. doi: 10.1016/s0140-6736(88)92744-4. [DOI] [PubMed] [Google Scholar]
  27. Watanabe T., Yamaguchi K., Takatsuki K., Osame M., Yoshida M. Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. J Exp Med. 1990 Sep 1;172(3):759–765. doi: 10.1084/jem.172.3.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Winter C. C., Carreno B. M., Turner R. V., Koenig S., Biddison W. E. The 45 pocket of HLA-A2.1 plays a role in presentation of influenza virus matrix peptide and alloantigens. J Immunol. 1991 May 15;146(10):3508–3512. [PubMed] [Google Scholar]
  29. Yoshida M., Osame M., Kawai H., Toita M., Kuwasaki N., Nishida Y., Hiraki Y., Takahashi K., Nomura K., Sonoda S. Increased replication of HTLV-I in HTLV-I-associated myelopathy. Ann Neurol. 1989 Sep;26(3):331–335. doi: 10.1002/ana.410260304. [DOI] [PubMed] [Google Scholar]

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