Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1994 May;68(5):3334–3342. doi: 10.1128/jvi.68.5.3334-3342.1994

An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans.

M Shirai 1, H Okada 1, M Nishioka 1, T Akatsuka 1, C Wychowski 1, R Houghten 1, C D Pendleton 1, S M Feinstone 1, J A Berzofsky 1
PMCID: PMC236824  PMID: 7512163

Abstract

Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C virus (HCV) proteins. CTL may play an important role in the control of infection by HCV. Here, we identify a highly conserved antigenic site in the HCV core recognized by both murine and human CTL. Spleen cells from mice immunized with a recombinant vaccinia virus expressing the HCV core gene were restimulated in vitro with 11 peptides from the core protein. CTL from H-2d mice responded to a single 16-residue synthetic peptide (HCV 129-144). This conserved epitope was presented by a murine class I major histocompatibility molecule (H-2Dd) to conventional CD4- CD8+ CTL mapped by using transfectants expressing Dd, Ld, or Kd, but was not seen by CTL restricted by H-2b. The murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL from two HCV-seropositive patients but not by CTL from any seronegative donors. CTL from two HLA-A2-positive patients with acute and chronic hepatitides C recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by HLA-A2 and containing an HLA-A2-binding motif, extending only 1 residue beyond the murine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a valuable component of an HCV vaccine against a broad range of HCV isolates. This study demonstrates that the screening for CTL epitopes in mice prior to human study may be useful.

Full text

PDF
3334

Selected References

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

  1. Abastado J. P., Jaulin C., Schutze M. P., Langlade-Demoyen P., Plata F., Ozato K., Kourilsky P. Fine mapping of epitopes by intradomain Kd/Dd recombinants. J Exp Med. 1987 Aug 1;166(2):327–340. doi: 10.1084/jem.166.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alter H. J., Purcell R. H., Shih J. W., Melpolder J. C., Houghton M., Choo Q. L., Kuo G. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med. 1989 Nov 30;321(22):1494–1500. doi: 10.1056/NEJM198911303212202. [DOI] [PubMed] [Google Scholar]
  3. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  4. Berzofsky J. A. Approaches and issues in the development of vaccines against HIV. J Acquir Immune Defic Syndr. 1991;4(5):451–459. [PubMed] [Google Scholar]
  5. Berzofsky J. A. Epitope selection and design of synthetic vaccines. Molecular approaches to enhancing immunogenicity and cross-reactivity of engineered vaccines. Ann N Y Acad Sci. 1993 Aug 12;690:256–264. doi: 10.1111/j.1749-6632.1993.tb44014.x. [DOI] [PubMed] [Google Scholar]
  6. Bodmer H. C., Pemberton R. M., Rothbard J. B., Askonas B. A. Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. Cell. 1988 Jan 29;52(2):253–258. doi: 10.1016/0092-8674(88)90514-4. [DOI] [PubMed] [Google Scholar]
  7. Boehncke W. H., Takeshita T., Pendleton C. D., Houghten R. A., Sadegh-Nasseri S., Racioppi L., Berzofsky J. A., Germain R. N. The importance of dominant negative effects of amino acid side chain substitution in peptide-MHC molecule interactions and T cell recognition. J Immunol. 1993 Jan 15;150(2):331–341. [PubMed] [Google Scholar]
  8. Bradley D. W., McCaustland K. A., Cook E. H., Schable C. A., Ebert J. W., Maynard J. E. Posttransfusion non-A, non-B hepatitis in chimpanzees. Physicochemical evidence that the tubule-forming agent is a small, enveloped virus. Gastroenterology. 1985 Mar;88(3):773–779. [PubMed] [Google Scholar]
  9. Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
  10. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. doi: 10.1126/science.2523562. [DOI] [PubMed] [Google Scholar]
  11. Clerici M., Lucey D. R., Zajac R. A., Boswell R. N., Gebel H. M., Takahashi H., Berzofsky J. A., Shearer G. M. Detection of cytotoxic T lymphocytes specific for synthetic peptides of gp160 in HIV-seropositive individuals. J Immunol. 1991 Apr 1;146(7):2214–2219. [PubMed] [Google Scholar]
  12. Cornette J. L., Margalit H., DeLisi C., Berzofsky J. A. Identification of T-cell epitopes and use in construction of synthetic vaccines. Methods Enzymol. 1989;178:611–634. doi: 10.1016/0076-6879(89)78042-3. [DOI] [PubMed] [Google Scholar]
  13. Corr M., Boyd L. F., Padlan E. A., Margulies D. H. H-2Dd exploits a four residue peptide binding motif. J Exp Med. 1993 Dec 1;178(6):1877–1892. doi: 10.1084/jem.178.6.1877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cristiano K., Di Bisceglie A. M., Hoofnagle J. H., Feinstone S. M. Hepatitis C viral RNA in serum of patients with chronic non-A, non-B hepatitis: detection by the polymerase chain reaction using multiple primer sets. Hepatology. 1991 Jul;14(1):51–55. doi: 10.1002/hep.1840140109. [DOI] [PubMed] [Google Scholar]
  15. De Groot A. S., Clerici M., Hosmalin A., Hughes S. H., Barnd D., Hendrix C. W., Houghten R., Shearer G. M., Berzofsky J. A. Human immunodeficiency virus reverse transcriptase T helper epitopes identified in mice and humans: correlation with a cytotoxic T cell epitope. J Infect Dis. 1991 Dec;164(6):1058–1065. doi: 10.1093/infdis/164.6.1058. [DOI] [PubMed] [Google Scholar]
  16. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Di Bisceglie A. M., Hoofnagle J. H. Therapy of chronic hepatitis C with alpha-interferon: the answer? Or more questions? Hepatology. 1991 Mar;13(3):601–603. doi: 10.1016/0270-9139(91)90318-p. [DOI] [PubMed] [Google Scholar]
  18. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  19. Elliott T., Cerundolo V., Elvin J., Townsend A. Peptide-induced conformational change of the class I heavy chain. Nature. 1991 May 30;351(6325):402–406. doi: 10.1038/351402a0. [DOI] [PubMed] [Google Scholar]
  20. Evans G. A., Margulies D. H., Shykind B., Seidman J. G., Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. doi: 10.1038/300755a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Farci P., Alter H. J., Govindarajan S., Wong D. C., Engle R., Lesniewski R. R., Mushahwar I. K., Desai S. M., Miller R. H., Ogata N. Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992 Oct 2;258(5079):135–140. doi: 10.1126/science.1279801. [DOI] [PubMed] [Google Scholar]
  23. Feinstone S. M., Alter H. J., Dienes H. P., Shimizu Y., Popper H., Blackmore D., Sly D., London W. T., Purcell R. H. Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis. 1981 Dec;144(6):588–598. doi: 10.1093/infdis/144.6.588. [DOI] [PubMed] [Google Scholar]
  24. Gammon G., Geysen H. M., Apple R. J., Pickett E., Palmer M., Ametani A., Sercarz E. E. T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes. J Exp Med. 1991 Mar 1;173(3):609–617. doi: 10.1084/jem.173.3.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Germain R. N., Margulies D. H. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi: 10.1146/annurev.iy.11.040193.002155. [DOI] [PubMed] [Google Scholar]
  26. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. He L. F., Alling D., Popkin T., Shapiro M., Alter H. J., Purcell R. H. Determining the size of non-A, non-B hepatitis virus by filtration. J Infect Dis. 1987 Oct;156(4):636–640. doi: 10.1093/infdis/156.4.636. [DOI] [PubMed] [Google Scholar]
  28. Hijikata M., Kato N., Ootsuyama Y., Nakagawa M., Ohkoshi S., Shimotohno K. Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun. 1991 Feb 28;175(1):220–228. doi: 10.1016/s0006-291x(05)81223-9. [DOI] [PubMed] [Google Scholar]
  29. Hosmalin A., Clerici M., Houghten R., Pendleton C. D., Flexner C., Lucey D. R., Moss B., Germain R. N., Shearer G. M., Berzofsky J. A. An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2344–2348. doi: 10.1073/pnas.87.6.2344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Houghton M., Weiner A., Han J., Kuo G., Choo Q. L. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology. 1991 Aug;14(2):381–388. [PubMed] [Google Scholar]
  32. Hunt D. F., Henderson R. A., Shabanowitz J., Sakaguchi K., Michel H., Sevilir N., Cox A. L., Appella E., Engelhard V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science. 1992 Mar 6;255(5049):1261–1263. doi: 10.1126/science.1546328. [DOI] [PubMed] [Google Scholar]
  33. Imawari M., Nomura M., Kaieda T., Moriyama T., Oshimi K., Nakamura I., Gunji T., Ohnishi S., Ishikawa T., Nakagama H. Establishment of a human T-cell clone cytotoxic for both autologous and allogeneic hepatocytes from chronic hepatitis patients with type non-A, non-B virus. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2883–2887. doi: 10.1073/pnas.86.8.2883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kato N., Hijikata M., Ootsuyama Y., Nakagawa M., Ohkoshi S., Sugimura T., Shimotohno K. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9524–9528. doi: 10.1073/pnas.87.24.9524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kiyosawa K., Sodeyama T., Tanaka E., Gibo Y., Yoshizawa K., Nakano Y., Furuta S., Akahane Y., Nishioka K., Purcell R. H. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990 Oct;12(4 Pt 1):671–675. doi: 10.1002/hep.1840120409. [DOI] [PubMed] [Google Scholar]
  36. Koziel M. J., Dudley D., Wong J. T., Dienstag J., Houghton M., Ralston R., Walker B. D. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol. 1992 Nov 15;149(10):3339–3344. [PubMed] [Google Scholar]
  37. Le A. X., Bernhard E. J., Holterman M. J., Strub S., Parham P., Lacy E., Engelhard V. H. Cytotoxic T cell responses in HLA-A2.1 transgenic mice. Recognition of HLA alloantigens and utilization of HLA-A2.1 as a restriction element. J Immunol. 1989 Feb 15;142(4):1366–1371. [PubMed] [Google Scholar]
  38. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  39. Margulies D. H., Evans G. A., Ozato K., Camerini-Otero R. D., Tanaka K., Appella E., Seidman J. G. Expression of H-2Dd and H-2Ld mouse major histocompatibility antigen genes in L cells after DNA-mediated gene transfer. J Immunol. 1983 Jan;130(1):463–470. [PubMed] [Google Scholar]
  40. Maéno M., Kaminaka K., Sugimoto H., Esumi M., Hayashi N., Komatsu K., Abe K., Sekiguchi S., Yano M., Mizuno K. A cDNA clone closely associated with non-A, non-B hepatitis. Nucleic Acids Res. 1990 May 11;18(9):2685–2689. doi: 10.1093/nar/18.9.2685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. McCluskey J., Boyd L., Foo M., Forman J., Margulies D. H., Bluestone J. A. Analysis of hybrid H-2D and L antigens with reciprocally mismatched aminoterminal domains: functional T cell recognition requires preservation of fine structural determinants. J Immunol. 1986 Dec 15;137(12):3881–3890. [PubMed] [Google Scholar]
  42. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L., Williams R. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982 Dec;129(6):2773–2778. [PubMed] [Google Scholar]
  43. Murre C., Choi E., Weis J., Seidman J. G., Ozato K., Liu L., Burakoff S. J., Reiss C. S. Dissection of serological and cytolytic T lymphocyte epitopes on murine major histocompatibility antigens by a recombinant H-2 gene separating the first two external domains. J Exp Med. 1984 Jul 1;160(1):167–178. doi: 10.1084/jem.160.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Naumov N. V., Mondelli M., Alexander G. J., Tedder R. S., Eddleston A. L., Williams R. Relationship between expression of hepatitis B virus antigens in isolated hepatocytes and autologous lymphocyte cytotoxicity in patients with chronic hepatitis B virus infection. Hepatology. 1984 Jan-Feb;4(1):63–68. doi: 10.1002/hep.1840040111. [DOI] [PubMed] [Google Scholar]
  45. Ogata N., Alter H. J., Miller R. H., Purcell R. H. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3392–3396. doi: 10.1073/pnas.88.8.3392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Okamoto H., Okada S., Sugiyama Y., Tanaka T., Sugai Y., Akahane Y., Machida A., Mishiro S., Yoshizawa H., Miyakawa Y. Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-noncoding region. Jpn J Exp Med. 1990 Aug;60(4):215–222. [PubMed] [Google Scholar]
  47. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pasternack M. S. Cytotoxic T-lymphocytes. Adv Intern Med. 1988;33:17–44. [PubMed] [Google Scholar]
  49. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell. 1987 Jan 30;48(2):231–240. doi: 10.1016/0092-8674(87)90426-0. [DOI] [PubMed] [Google Scholar]
  50. Prince A. M., Brotman B., Huima T., Pascual D., Jaffery M., Inchauspé G. Immunity in hepatitis C infection. J Infect Dis. 1992 Mar;165(3):438–443. doi: 10.1093/infdis/165.3.438. [DOI] [PubMed] [Google Scholar]
  51. Realdi G., Alberti A., Rugge M., Rigoli A. M., Tremolada F., Schivazappa L., Ruol A. Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis. Gut. 1982 Apr;23(4):270–275. doi: 10.1136/gut.23.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Reddehase M. J., Rothbard J. B., Koszinowski U. H. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature. 1989 Feb 16;337(6208):651–653. doi: 10.1038/337651a0. [DOI] [PubMed] [Google Scholar]
  53. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  54. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  56. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  57. Shirai M., Akatsuka T., Pendleton C. D., Houghten R., Wychowski C., Mihalik K., Feinstone S., Berzofsky J. A. Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C virus nonstructural RNA polymerase-like protein. J Virol. 1992 Jul;66(7):4098–4106. doi: 10.1128/jvi.66.7.4098-4106.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Shirai M., Pendleton C. D., Berzofsky J. A. Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. J Immunol. 1992 Mar 15;148(6):1657–1667. [PubMed] [Google Scholar]
  59. Takahashi H., Cohen J., Hosmalin A., Cease K. B., Houghten R., Cornette J. L., DeLisi C., Moss B., Germain R. N., Berzofsky J. A. An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1988 May;85(9):3105–3109. doi: 10.1073/pnas.85.9.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Takahashi H., Houghten R., Putney S. D., Margulies D. H., Moss B., Germain R. N., Berzofsky J. A. Structural requirements for class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein. J Exp Med. 1989 Dec 1;170(6):2023–2035. doi: 10.1084/jem.170.6.2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Takahashi H., Merli S., Putney S. D., Houghten R., Moss B., Germain R. N., Berzofsky J. A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118–121. doi: 10.1126/science.2789433. [DOI] [PubMed] [Google Scholar]
  62. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  63. Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
  64. Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. J Exp Med. 1989 Apr 1;169(4):1421–1434. doi: 10.1084/jem.169.4.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  66. Weiner A. J., Brauer M. J., Rosenblatt J., Richman K. H., Tung J., Crawford K., Bonino F., Saracco G., Choo Q. L., Houghton M. Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology. 1991 Feb;180(2):842–848. doi: 10.1016/0042-6822(91)90104-j. [DOI] [PubMed] [Google Scholar]
  67. Weiner A. J., Geysen H. M., Christopherson C., Hall J. E., Mason T. J., Saracco G., Bonino F., Crawford K., Marion C. D., Crawford K. A. Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3468–3472. doi: 10.1073/pnas.89.8.3468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  69. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES