Abstract
This communication deals with the question of which of the viral antigens constitutes the targets for cytotoxic T lymphocytes (CTL) generated against herpes simplex virus type 1 (HSV-1). The approach used was, first, to compare cytotoxicity of CTL against target cells infected with virus in the presence of tunicamycin and 2-deoxy-D-glucose, which are known to inhibit glycoprotein synthesis, and second, to compare cytotoxicity of CTL against target cells infected with wild-type HSV-1 with that against target cells infected with a temperature-sensitive mutant of HSV-1 which, at the nonpermissive temperature, exhibits diminished glycoprotein synthesis. The results show that glycoprotein expression is required for the demonstration of cytotoxic activity of CTL. The level of cytotoxicity against the temperature-sensitive HSV-1 target at the nonpermissive temperature was reduced and correlated with the level of expression of the major envelope glycoprotein region (VP123; molecular weight = 123,000) at the target cell surface as measured serologically by antibody binding studies. The results were interpreted to indicate that HSV-1-induced glycoproteins are the target antigens for anti-HSV CTL and that the principal viral antigens recognized by the CTL may be glycoproteins of the VP123 region.
Full text
PDF![451](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/41c63c6f7e1a/iai00179-0131.png)
![452](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/a979cb3b49d9/iai00179-0132.png)
![453](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/921276219c5a/iai00179-0133.png)
![454](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/1f2f42b09f74/iai00179-0134.png)
![455](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/6dc179ba0017/iai00179-0135.png)
![456](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/da2d7ef943cb/iai00179-0136.png)
![457](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/d1b856abe9ba/iai00179-0137.png)
![458](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/94b9c4715420/iai00179-0138.png)
![459](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/4445a82b6634/iai00179-0139.png)
![460](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/5243bd15cec1/iai00179-0140.png)
![461](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3b/551334/a9bf6cdc14aa/iai00179-0141.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alkan S. S., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response: the capacity of L-tyrosine-azobenzenearsonate to serve as a carrier for a macromolecular hapten. J Immunol. 1971 Aug;107(2):353–358. [PubMed] [Google Scholar]
- Ballas Z. K., Henney C. S. Generation of H-2 restricted cytotoxic T cells by trinitrophenylated proteins in vitro: specificity and requirements. J Immunol. 1979 Oct;123(4):1696–1704. [PubMed] [Google Scholar]
- Blanden R. V. T cell response to viral and bacterial infection. Transplant Rev. 1974;19(0):56–88. doi: 10.1111/j.1600-065x.1974.tb00128.x. [DOI] [PubMed] [Google Scholar]
- Bone D. R., Courtney R. J. A temperature-sensitive mutant of herpes simplex virus type 1 defective in the synthesis of the major capsid polypeptide. J Gen Virol. 1974 Jul;24(1):17–27. doi: 10.1099/0022-1317-24-1-17. [DOI] [PubMed] [Google Scholar]
- Braciale T. J. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. doi: 10.1016/0008-8749(77)90170-8. [DOI] [PubMed] [Google Scholar]
- Braciale T. J. Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells. J Exp Med. 1977 Sep 1;146(3):673–689. doi: 10.1084/jem.146.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
- Cohen G. H., Katze M., Hydrean-Stern C., Eisenberg R. J. Type-common CP-1 antigen of herpes simplex virus is associated with a 59,000-molecular-weight envelope glycoprotein. J Virol. 1978 Jul;27(1):172–181. doi: 10.1128/jvi.27.1.172-181.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Courtney R. J., Benyesh-Melnick M. Isolation and characterization of a large molecular-weight polypeptide of herpes simplex virus type 1. Virology. 1974 Dec;62(2):539–551. doi: 10.1016/0042-6822(74)90414-0. [DOI] [PubMed] [Google Scholar]
- Courtney R. J., McCombs R. M., Benyesh-Melnick M. Antigens specified by herpesviruses. II. Effect of arginine deprivation on the synthesis of cytoplasmic and nuclear proteins. Virology. 1971 Feb;43(2):356–365. doi: 10.1016/0042-6822(71)90308-4. [DOI] [PubMed] [Google Scholar]
- Courtney R. J., Steiner S. M., Benyesh-Melnick M. Effects of 2-deoxy-D-glucose on herpes simplex virus replication. Virology. 1973 Apr;52(2):447–455. doi: 10.1016/0042-6822(73)90340-1. [DOI] [PubMed] [Google Scholar]
- Dennert G. Thymus derived killer cells: specificity of function, and antigen recognition. Transplant Rev. 1976;29:59–88. doi: 10.1111/j.1600-065x.1976.tb00197.x. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
- Drake W. P., Ungaro P. C., Mardiney M. R., Jr Preservation of cellular antigenicity of tumor cells by the use of formalin fixation. Cancer Res. 1972 May;32(5):1042–1044. [PubMed] [Google Scholar]
- Eberle R., Courtney R. J. Preparation and characterization of specific antisera to individual glycoprotein antigens comprising the major glycoprotein region of herpes simplex virus type 1. J Virol. 1980 Sep;35(3):902–917. doi: 10.1128/jvi.35.3.902-917.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Effros R. B., Doherty P. C., Gerhard W., Bennink J. Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses. J Exp Med. 1977 Mar 1;145(3):557–568. doi: 10.1084/jem.145.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ennis F. A., Martin W. J., Verbonitz M. W. Hemagglutinin-specific cytotoxic T-cell response during influenza infection. J Exp Med. 1977 Sep 1;146(3):893–898. doi: 10.1084/jem.146.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forman J. The specificity of thymus-derived T-cells in cell-mediated cytotoxic reactions. Transplant Rev. 1976;29:146–163. doi: 10.1111/j.1600-065x.1976.tb00200.x. [DOI] [PubMed] [Google Scholar]
- GELL P. G., BENACERRAF B. Studies on hypersensitivity. II. Delayed hypersensitivity to denatured proteins in guinea pigs. Immunology. 1959 Jan;2(1):64–70. [PMC free article] [PubMed] [Google Scholar]
- Glorioso J. C., Wilson L. A., Fenger T. W., Smith J. W. Complement-mediated cytolysis of HSV-1 and HSV-2 infected cells: plasma membrane antigens reactive with type-specific and cross-reactive antibody. J Gen Virol. 1978 Aug;40(2):443–454. doi: 10.1099/0022-1317-40-2-443. [DOI] [PubMed] [Google Scholar]
- Gooding L. R. Antibody blockade of lysis by T lymphocyte effectors generated against syngeneic SV40 transformed cells. J Immunol. 1979 Jun;122(6):2328–2336. [PubMed] [Google Scholar]
- Hale A. H., Witte O. N., Baltimore D., Eisen H. N. Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1978 Feb;75(2):970–974. doi: 10.1073/pnas.75.2.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heine J. W., Spear P. G., Roizman B. Proteins specified by herpes simplex virus. VI. Viral proteins in the plasma membrane. J Virol. 1972 Mar;9(3):431–439. doi: 10.1128/jvi.9.3.431-439.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herrmann S. H., Mescher M. F. Purification of the H-2Kk molecule of the murine major histocompatibility complex. J Biol Chem. 1979 Sep 25;254(18):8713–8716. [PubMed] [Google Scholar]
- Jackson D. C., Ada G. L., Hapel A. J., Dunlop M. B. Changes in the surface of virus-infected cells recognized by cytotoxic T cells. II. A requirement for glycoprotein synthesis in virus-infected target cells. Scand J Immunol. 1976;5(9):1021–1029. doi: 10.1111/j.1365-3083.1976.tb03054.x. [DOI] [PubMed] [Google Scholar]
- Janeway C. A., Jr The specificity of T lymphocyte responses to chemically defined antigens. Transplant Rev. 1976;29:164–188. doi: 10.1111/j.1600-065x.1976.tb00201.x. [DOI] [PubMed] [Google Scholar]
- Koszinowski U. H., Allen H., Gething M. J., Waterfield M. D., Klenk H. D. Recognition of viral glycoproteins by influenza A-specific cross-reactive cytolytic T lymphocytes. J Exp Med. 1980 Apr 1;151(4):945–958. doi: 10.1084/jem.151.4.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawman M. J., Rouse B. T., Courtney R. J., Walker R. D. Cell-mediated immunity against herpes simplex induction of cytotoxic T lymphocytes. Infect Immun. 1980 Jan;27(1):133–139. doi: 10.1128/iai.27.1.133-139.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leavitt R., Schlesinger S., Kornfeld S. Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses. J Virol. 1977 Jan;21(1):375–385. doi: 10.1128/jvi.21.1.375-385.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKenzie I. F., Pang T., Blanden R. V. The use of H-2 mutants as models for the study of T cell activation. Immunol Rev. 1977;35:179–230. [PubMed] [Google Scholar]
- Moss B., Rosenblum E. N. Hydroxylapatite chromatography of protein-sodium dodecyl sulfate complexes. A new method for the separation of polypeptide subunits. J Biol Chem. 1972 Aug 25;247(16):5194–5198. [PubMed] [Google Scholar]
- Norrild B., Ludwig H., Rott R. Identification of a common antigen of herpes simplex virus bovine herpes mammillitis virus, and B virus. J Virol. 1978 Jun;26(3):712–717. doi: 10.1128/jvi.26.3.712-717.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norrild B., Vestergaard B. F. Polyacrylamide gel electrophoretic analysis of herpes simplex virus type 1 immunoprecipitates obtained by quantitative immunoelectrophoresis in antibody-containing agarose gel. J Virol. 1977 Apr;22(1):113–117. doi: 10.1128/jvi.22.1.113-117.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Notkins A. L. Immune mechanisms by which the spread of viral infections is stopped. Cell Immunol. 1974 Mar 30;11(1-3):478–483. doi: 10.1016/0008-8749(74)90045-8. [DOI] [PubMed] [Google Scholar]
- Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
- Olshevsky U., Becker Y. Surface glycopeptides in the envelope of herpes simplex virions. Virology. 1972 Oct;50(1):277–279. doi: 10.1016/0042-6822(72)90371-6. [DOI] [PubMed] [Google Scholar]
- Pfizenmaier K., Jung H., Starzinski-Powitz A., Röllinghoff M., Wagner H. The role of T cells in anti-herpes simplex virus immunity. I. Induction of antigen-specific cytotoxic T lymphocytes. J Immunol. 1977 Sep;119(3):939–944. [PubMed] [Google Scholar]
- Rouse B. T., Babiuk L. A. Mechanisms of recovery from Herpesvirus infections -a review. Can J Comp Med. 1978 Oct;42(4):414–427. [PMC free article] [PubMed] [Google Scholar]
- Schaffer P. A., Courtney R. J., McCombs R. M., Benyesh-Melnick M. A temperature-sensitive mutant of herpes simplex virus defective in glycoprotein synthesis. Virology. 1971 Nov;46(2):356–368. doi: 10.1016/0042-6822(71)90037-7. [DOI] [PubMed] [Google Scholar]
- Spear P. G. Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells. J Virol. 1976 Mar;17(3):991–1008. doi: 10.1128/jvi.17.3.991-1008.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stulting R. D., Todd R. F., 3rd, Gooding L. R. Susceptibility of anti-H-2-capped target cells to humoral and T lymphocyte-mediated lysis. Transplantation. 1976 Jan;21(1):71–73. doi: 10.1097/00007890-197601000-00013. [DOI] [PubMed] [Google Scholar]
- Thorn R. M., Henney C. S. Studies on the mechanism of lymphocyte-mediated cytolysis. VI. A reappraisal of the requirement for protein synthesis during T cell-mediated lysis. J Immunol. 1976 Jan;116(1):146–149. [PubMed] [Google Scholar]
- Zinkernagel R. M. Speculations on the role of major transplantation antigens in cell-mediated immunity against intracellular parasites. Curr Top Microbiol Immunol. 1978;82:113–138. doi: 10.1007/978-3-642-46388-4_4. [DOI] [PubMed] [Google Scholar]
- Zweerink H. J., Askonas B. A., Millican D., Courtneidge S. A., Skehel J. J. Cytotoxic T cells to type A influenza virus; viral hemagglutinin induces A-strain specificity while infected cells confer cross-reactive cytotoxicity. Eur J Immunol. 1977 Sep;7(9):630–635. doi: 10.1002/eji.1830070910. [DOI] [PubMed] [Google Scholar]
- Zweerink H. J., Courtneidge S. A., Skehel J. J., Crumpton M. J., Askonas B. A. Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses. Nature. 1977 May 26;267(5609):354–356. doi: 10.1038/267354a0. [DOI] [PubMed] [Google Scholar]