Abstract
Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.
Full Text
The Full Text of this article is available as a PDF (1.5 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adler W. H., Takiguchi T., Marsh B., Smith R. T. Cellular recognition by mouse lymphocytes in vitro. II. Specific stimulation by histocompatibility antigens in mixed cell culture. J Immunol. 1970 Oct;105(4):984–1000. [PubMed] [Google Scholar]
- Bevan M. J. Interaction antigens detected by cytotoxic T cells with the major histocompatibility complex as modifier. Nature. 1975 Jul 31;256(5516):419–421. doi: 10.1038/256419a0. [DOI] [PubMed] [Google Scholar]
- Blanden R. V., Doherty P. C., Dunlop M. B., Gardner I. D., Zinkernagel R. M., David C. S. Genes required for cytotoxicity against virus-infected target cells in K and D regions of H-2 complex. Nature. 1975 Mar 20;254(5497):269–270. doi: 10.1038/254269a0. [DOI] [PubMed] [Google Scholar]
- Blank K. J., Freedman H. A., Lilly F. T-lymphocytes response to Friend virus-induced tumour cell lines in mice of strains congenic at H--2. Nature. 1976 Mar 18;260(5548):250–252. doi: 10.1038/260250a0. [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]
- Forman J., Möller G. Generation of cytotoxic lymphocytes in mixed lymphocyte reactions. I. Specificity of the effector cells. J Exp Med. 1973 Sep 1;138(3):672–685. doi: 10.1084/jem.138.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forman J. On the role of the H-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets. J Exp Med. 1975 Aug 1;142(2):403–418. doi: 10.1084/jem.142.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Germain R. N., Dorf M. E., Benacerraf B. Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor. J Exp Med. 1975 Oct 1;142(4):1023–1028. doi: 10.1084/jem.142.4.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gomard E., Duprez V., Henin Y., Levy J. P. H-2 region product as determinant in immune cytolysis of syngeneic tumour cells by anti-MSV T lymphocytes. Nature. 1976 Apr 22;260(5553):707–709. doi: 10.1038/260707a0. [DOI] [PubMed] [Google Scholar]
- Gordon R. D., Simpson E., Samelson L. E. In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice. J Exp Med. 1975 Nov 1;142(5):1108–1120. doi: 10.1084/jem.142.5.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henning R., Schrader J. W., Edelman G. M. Antiviral antibodies inhibit the lysis of tumour cells by anti-H--2 sera. Nature. 1976 Oct 21;263(5579):689–691. doi: 10.1038/263689a0. [DOI] [PubMed] [Google Scholar]
- Klenk H. D., Choppin P. W. Glycosphingolipids of plasma membranes of cultured cells and an enveloped virus (SV5) grown in these cells. Proc Natl Acad Sci U S A. 1970 May;66(1):57–64. doi: 10.1073/pnas.66.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohn A. The fate of protein subunits of parainfluenza (Sendai) virus after adsorption to NIL8 hamster embryo cells. J Gen Virol. 1975 Nov;29(2):179–187. doi: 10.1099/0022-1317-29-2-179. [DOI] [PubMed] [Google Scholar]
- Koszinowski U., Ertl H. Lysis mediated by T cells and restricted by H-2 antigen of target cells infected with vaccinia virus. Nature. 1975 Jun 12;255(5509):552–554. doi: 10.1038/255552a0. [DOI] [PubMed] [Google Scholar]
- Koszinowski U., Ertl H. Role of early viral surface antigens in cellular immune response to vaccinia virus. Eur J Immunol. 1976 Oct;6(10):679–683. doi: 10.1002/eji.1830061004. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lamb R. A., Mahy B. W., Choppin P. W. The synthesis of sendai virus polypeptides in infected cells. Virology. 1976 Jan;69(1):116–131. doi: 10.1016/0042-6822(76)90199-9. [DOI] [PubMed] [Google Scholar]
- Morgan C., Howe C. Structure and development of viruses as observed in the electron microscope. IX. Entry of parainfluenza I (Sendai) virus. J Virol. 1968 Oct;2(10):1122–1132. doi: 10.1128/jvi.2.10.1122-1132.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Möller G., Sjöberg O., Andersson J. Mitogen-induced lymphocyte-mediated cytotoxicity in vitro: effect of mitogens selectively activating T or B cells. Eur J Immunol. 1972 Dec;2(6):586–592. doi: 10.1002/eji.1830020621. [DOI] [PubMed] [Google Scholar]
- Okada Y., Kim J., Maeda Y., Koseki I. Specific movement of cell membranes fused with HVJ (Sendai virus). Proc Natl Acad Sci U S A. 1974 May;71(5):2043–2047. doi: 10.1073/pnas.71.5.2043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfizenmaier K., Strazinski-Powitz A., Rodt H., Röllinghoff M., Wagner H. Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells. J Exp Med. 1976 Apr 1;143(4):999–1004. doi: 10.1084/jem.143.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson W. S. Ribonucleic acid polymerase activity in Sendai virions and nucleocapsid. J Virol. 1971 Jul;8(1):81–86. doi: 10.1128/jvi.8.1.81-86.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schrader J. W., Cunningham B. A., Edelman G. M. Functional interactions of viral and histocompatibility antigens at tumor cell surfaces. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5066–5070. doi: 10.1073/pnas.72.12.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schrader J. W., Edelman G. M. Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells. J Exp Med. 1976 Mar 1;143(3):601–614. doi: 10.1084/jem.143.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shellam G. R., Knight R. A., Mitchison N. A., Gorczynski R. M., Maoz A. The specificity of effector T cells activated by tumours induced by murine oncornaviruses. Transplant Rev. 1976;29:249–276. doi: 10.1111/j.1600-065x.1976.tb00204.x. [DOI] [PubMed] [Google Scholar]
- Wagner H., Röllinghoff M. T cell-mediated cytotoxicity: discrimination between antigen recognition, lethal hit and cytolysis phase. Eur J Immunol. 1974 Nov;4(11):745–750. doi: 10.1002/eji.1830041108. [DOI] [PubMed] [Google Scholar]
- Waterfield J. D., Waterfield E. M., Möller G. Lymphocyte-mediated cytotoxicity against tumor cells. I. Con A activated cytotoxic effector cells exhibit immunological specificity. Cell Immunol. 1975 Jun;17(2):392–404. doi: 10.1016/s0008-8749(75)80043-8. [DOI] [PubMed] [Google Scholar]
- Woodruff J. F., Woodruff J. J. T lymphocyte interaction with viruses and virus-infected tissues. Prog Med Virol. 1975;19:120–160. [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M. Virus-specific T-cell-mediated cytotoxicity across the H-2 barrier to virus-altered alloantigen. Nature. 1976 May 13;261(5556):139–141. doi: 10.1038/261139a0. [DOI] [PubMed] [Google Scholar]