Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1975 Dec 1;142(6):1339–1348. doi: 10.1084/jem.142.6.1339

Recognitive specificity of human cytotoxic T lymphocytes. I. Antigen- specific inhibition of human cell-mediated lympholysis

PMCID: PMC2190082  PMID: 53262

Abstract

The specificity of antigen recognition by in vitro sensitized human cytotoxic T lymphocytes (CTLs) has been studied using a sensitive cell- mediated lympholysis (CML) assay. Frequently, high levels of cytotoxicity are observed on third-party targets unrelated to sensitizing or responding cells; however, no cytotoxicity differing significantly from zero has been observed on targets autologous to the responding CTLs. This "cross-killing" of third-party target cells has been observed when stimulating and third-party cells bear no cross- reacting serologically defined (SD) antigens, thought to be the target antigens recognized by CTLs. CML-blocking studies, using unlabeled normal human lymphocytes to inhibit 51Cr release from radiolabeled target cells, have shown that cross-killing, even in the absence of shared SD determinants, results from CTLs recognizing antigens shared by the third-party targets and the initial stimulating population. Furthermore, these antigens have been mapped to the major histocompatibility complex (MHC). The ability of human CTLs to specifically recognize MHC-controlled antigens not detected serologically suggests that SD antigens may be recognized differently by alloantisera and CTLs, or that MHC antigens other than SD may be the targets of CTLs in CML.

Full Text

The Full Text of this article is available as a PDF (694.0 KB).

Selected References

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

  1. Bach F. H., Bach M. L., Sondel P. M., Sundharadas G. Genetic control of mixed leukocyte culture reactivity. Transplant Rev. 1972;12:30–56. doi: 10.1111/j.1600-065x.1972.tb00052.x. [DOI] [PubMed] [Google Scholar]
  2. Bach F. H., Segall M., Zier K. S., Sondel P. M., Alter B. J., Bach M. L. Cell mediated immunity: separation of cells involved in recognitive and destructive phases. Science. 1973 Apr 27;180(4084):403–406. doi: 10.1126/science.180.4084.403. [DOI] [PubMed] [Google Scholar]
  3. Bach F. H., Zier K. S., Sondel P. M. The nature of cells responding in mixed leukocyte cultures and cell-mediated lympholysis. Transplant Proc. 1973 Dec;5(4):1717–1720. [PubMed] [Google Scholar]
  4. Bevan M. J. Alloimmune cytotoxic T cells: Evidence that they recognize serologically defined antigens and bear clonally restricted receptors. J Immunol. 1975 Jan;114(1 Pt 2):316–319. [PubMed] [Google Scholar]
  5. Bonnard G. D., Chappuis M., Glauser A., Mempel W., Baumann P., Grosse-Wilde H., Albert E. D. SD vs. LD antigens as targets for lymphocyte-mediated cytotoxicity: study of a family presenting a recombination event within the MHR. Transplant Proc. 1973 Dec;5(4):1679–1682. [PubMed] [Google Scholar]
  6. Brondz B. D., Egorov I. K., Drizlikh G. I. Private specificities of H-2K and H-2D loci as possible selective targets for effector lymphocytes in cell-mediated immunity. J Exp Med. 1975 Jan 1;141(1):11–26. doi: 10.1084/jem.141.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Canty T. G., Wunderlich J. R., Fletcher F. Qualitative and quantitative studies of cytotoxic immune cells. J Immunol. 1971 Jan;106(1):200–208. [PubMed] [Google Scholar]
  8. Eijsvoogel V. P., du Bois M. J., Meinesz A., Bierhorst-Eijlander A., Zeylemaker W. P., Schellekens P. T. The specificty and the activation mechanism of cell-mediated lympholysis (CML) in man. Transplant Proc. 1973 Dec;5(4):1675–1678. [PubMed] [Google Scholar]
  9. Hartzman R. J., Segall M., Bach M. L., Bach F. H. Histocompatibility matching. VI. Miniaturization of the mixed leukocyte culture test: a preliminary report. Transplantation. 1971 Mar;11(3):268–273. doi: 10.1097/00007890-197103000-00005. [DOI] [PubMed] [Google Scholar]
  10. Hollander N., Ginsburg H. Specific adherence of in vitro differentiated lymphocytes to target cells. J Exp Med. 1972 Dec 1;136(6):1344–1355. doi: 10.1084/jem.136.6.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Häyry P., Andersson L. C., Nordling S., Virolainen M. Allograft response in vitro. Transplant Rev. 1972;12:91–140. doi: 10.1111/j.1600-065x.1972.tb00054.x. [DOI] [PubMed] [Google Scholar]
  12. Häyry P., Defendi V. Mixed lymphocyte cultures produce effector cells: model in vitro for allograft rejection. Science. 1970 Apr 3;168(3927):133–135. doi: 10.1126/science.168.3927.133. [DOI] [PubMed] [Google Scholar]
  13. Kristensen T., Grunnet N., Kissmeyer-Nielsen F. Cell mediated lympholysis in man. Occurrence of unexpected, HL-A (LA and FOUR) irrelevant lympholysis. Tissue Antigens. 1974;4(4):378–382. doi: 10.1111/j.1399-0039.1974.tb00264.x. [DOI] [PubMed] [Google Scholar]
  14. Lightbody J., Bernoco D., Miggiano V. C., Ceppellini R. Cell mediated lympholysis in man after sensitization of effector lymphocytes through mixed leukocyte cultures. G Batteriol Virol Immunol. 1971 Sep-Dec;64(9):243–254. [PubMed] [Google Scholar]
  15. Mayr W. R., Bernoco D., De Marchi M., Ceppellini R. Genetic analysis and biological properties of products of the third SD (AJ) locus of the HL-A region. Transplant Proc. 1973 Dec;5(4):1581–1593. [PubMed] [Google Scholar]
  16. Mittal K. K., Terasaki P. I. Serological cross-reactivity in the HL-A system. Tissue Antigens. 1974;4(2):146–156. doi: 10.1111/j.1399-0039.1974.tb00235.x. [DOI] [PubMed] [Google Scholar]
  17. Rosenberg E. B., McCoy J. L., Green S. S., Donnelly F. C., Siwarski D. F., Levine P. H., Herberman R. B. Destruction of human lymphoid tissue-culture cell lines by human peripheral lymphocytes in 51Cr-release cellular cytotoxicity assays. J Natl Cancer Inst. 1974 Feb;52(2):345–352. doi: 10.1093/jnci/52.2.345. [DOI] [PubMed] [Google Scholar]
  18. Solliday S., Bach F. H. Cytotoxicity: specificity after in vitro sensitization. Science. 1970 Dec 25;170(3965):1406–1409. doi: 10.1126/science.170.3965.1406. [DOI] [PubMed] [Google Scholar]
  19. Sondel P. M., Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. III. Specific allogeneic lympholysis mediated by human T cells alone. J Immunol. 1975 Mar;114(3):982–987. [PubMed] [Google Scholar]
  20. Svedmyr E. A., Hodes R. J. On the specificity of cell-mediated cytotoxicity in vitro. Cell Immunol. 1970 Dec;1(6):644–654. doi: 10.1016/0008-8749(70)90029-8. [DOI] [PubMed] [Google Scholar]
  21. TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
  22. Willumsen J., Heron I. Cell mediated lympholysis in man. A case of "non relevant" killing of third party persons. Tissue Antigens. 1974;4(2):172–177. doi: 10.1111/j.1399-0039.1974.tb00238.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES