Abstract
Cytotoxic T lymphocytes were generated in vitro against H-2 compatible or syngeneic tumor cells. In vitro cytotoxic activity was inhibited by specific anti-H2 sera, suggesting that H-2 antigens are involved in cell lysis. Two observations directly demonstrated the participation of the H-2 antigens on the tumor cells in their lysis by H-2-compatible T cells. First, coating of the H-2 antigens on the target tumor cell reduced the number of cells lysed on subsequent exposure to cytotoxic T cells. Second, when cytotoxic T cells were activated against an H-2 compatible tumor and assayed against an H-2-incompatible tumor, anti-H- 2 serum that could bind to the target cell, but not to the cytotoxic lymphocyte, inhibited lysis. H-2 antigens were also shown to be present on the cytotoxic lymphocytes. Specific antisera reacting with these H-2 antigens, but not those of the target cell, failed to inhibit lysis when small numbers of effector cells were assayed against H-2- incompatible target cells or when effector cells of F1-hybrid origin and bearing two H-2 haplotypes were assayed against a tumor cell of one of the parental strains. These findings suggest that it is the H-2 antigens on the tumor cell and not those on the cytotoxic lymphocytes that are important in cell-mediated lysis of H-2-compatible tumor cells.
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alter B. J., Schendel D. J., Bach M. L., Bach F. H., Klein J., Stimpfling J. H. Cell-mediated lympholysis. Importance of serologically defined H-2 regions. J Exp Med. 1973 May 1;137(5):1303–1309. doi: 10.1084/jem.137.5.1303. [DOI] [PMC free article] [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]
- Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [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]
- Doherty P. C., Zinkernagel R. M., Ramshaw I. A. Specificity and development of cytotoxic thymus-derived lymphocytes in lymphocytic choriomeningitis. J Immunol. 1974 Apr;112(4):1548–1552. [PubMed] [Google Scholar]
- Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
- Dunkley M., Miller R. G., Shortman K. A modified 51Cr release assay for cytotoxic lymphocytes. J Immunol Methods. 1974 Dec;6(1-2):39–51. doi: 10.1016/0022-1759(74)90088-x. [DOI] [PubMed] [Google Scholar]
- Ekidin M., Henney C. S. The effect of capping H-2 antigens on the susceptibility of target cells to humoral and T cell-mediated lysis. Nat New Biol. 1973 Nov 14;246(150):47–49. doi: 10.1038/newbio246047a0. [DOI] [PubMed] [Google Scholar]
- Faanes R. B., Choi Y. S., Good R. A. Escape from isoantiserum inhibition of lymphocyte-mediated cytotoxicity. J Exp Med. 1973 Jan 1;137(1):171–182. doi: 10.1084/jem.137.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Festenstein H., Abbasi K., Sachs J. A., Oliver R. T. Serologically undetectable immune responses in transplantation. Transplant Proc. 1972 Jun;4(2):219–222. [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]
- Henning R., Milner R. J., Reske K., Cunningham B. A., Edelman G. M. Subunit structure, cell surface orientation, and partial amino-acid sequences of murine histocompatibility antigens. Proc Natl Acad Sci U S A. 1976 Jan;73(1):118–122. doi: 10.1073/pnas.73.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirsch M. S., Phillips S. M., Solnik C., Black P. H., Schwartz R. S., Carpenter C. B. Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions in vitro. Proc Natl Acad Sci U S A. 1972 May;69(5):1069–1072. doi: 10.1073/pnas.69.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein P. A. Anomalous reactions of mouse alloantisera with cultured tumor cells. I. Demonstration of widespread occurrence using reference typing sera. J Immunol. 1975 Nov;115(5):1254–1260. [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., Thomssen R. Target cell-dependent T cell-mediated lysis of vaccinia virus-infected cells. Eur J Immunol. 1975 Apr;5(4):245–251. doi: 10.1002/eji.1830050405. [DOI] [PubMed] [Google Scholar]
- Lindahl K. F., Bach F. H. Human lymphocytes recognise mouse alloantigens. Nature. 1975 Apr 17;254(5501):607–609. doi: 10.1038/254607a0. [DOI] [PubMed] [Google Scholar]
- Nabholz M., Vives J., Young H. M., Meo T., Miggiano V., Rijnbeek A., Shreffler D. C. Cell-mediated cell lysis in vitro: genetic control of killer cell production and target specificities in the mouse. Eur J Immunol. 1974 May;4(5):378–387. doi: 10.1002/eji.1830040514. [DOI] [PubMed] [Google Scholar]
- Peck A. B., Bach F. H. Mouse cell-mediated lympholysis assay in serum-free and mouse serum-supplemented media: culture conditions and genetic factors. Scand J Immunol. 1975;4(1):53–62. doi: 10.1111/j.1365-3083.1975.tb02599.x. [DOI] [PubMed] [Google Scholar]
- Plata F., Cerottini J. C., Brunner K. T. Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Eur J Immunol. 1975 Apr;5(4):227–233. doi: 10.1002/eji.1830050402. [DOI] [PubMed] [Google Scholar]
- Rouse B. T., Röllinghoff M., Warner N. L. Anti-theta serum-induced supression of the cellular transfer of tumour-specific immunity to a syngeneic plasma cell tumour. Nat New Biol. 1972 Jul 26;238(82):116–117. doi: 10.1038/newbio238116a0. [DOI] [PubMed] [Google Scholar]
- Röllinghoff M., Pfizenmeier K., Trostmann H., Wagner H. T cell proliferation in the mixed lymphocyte culture does not necessarily result in the generation of cytotoxic T effector cells. Eur J Immunol. 1975 Aug;5(8):560–564. doi: 10.1002/eji.1830050811. [DOI] [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]
- Schwartz B. D., Nathenson S. G. Isolation of H-2 alloantigens solubilized by the detergent NP-40. J Immunol. 1971 Nov;107(5):1363–1367. [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., Doherty P. C. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature. 1974 Oct 11;251(5475):547–548. doi: 10.1038/251547a0. [DOI] [PubMed] [Google Scholar]