Abstract
A murine monoclonal antibody, 13.1, which blocks human natural killer (NK) cell-mediated lysis, has been developed. Hybridoma 13.1 was derived by fusion of NS-1 cells with spleen cells from mice immunized with an enriched population of NK cells. Supernatants of growing hybridomas were screened for their ability to block NK cell-mediated lysis of K562 targets. Antibody 13.1 is an IgG1 with a single light chain type and it does not fix complement. The 13.1 antigen is expressed on all peripheral blood mononuclear cells, with an antigen density approximately 1/30th that of HLA antigen heavy chain. Pretreatment and washing experiments revealed that inhibition of cytotoxicity occurred at the effector cell level only. Significant blocking was achieved with nanogram quantities of antibody and was not due to toxic effects on NK cells. Likewise, controls with other antibodies of the same subclass demonstrated that blocking was not a consequence of mere binding to NK cells. When a panel of 17 NK cell-susceptible targets was tested, the lysis of only 5 of these was blocked, namely K562, HL-60, KG-1, Daudi, and HEL, a human erythroleukemic cell line. The lysis of 12 human B cell and T cell line targets was not inhibited. In addition to the demonstration that the 13.1 antigen is a crucial cell surface structure involved in NK lysis, a heterogeneity of target cell recognition has been revealed that argues for the proposition that individual NK cells have multiple recognitive capabilities.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
- Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
- Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
- Clark E. A., Sturge J. C. Phylogeny of NK cell reactivity against human and nonhuman primate lymphoblastoid cell lines: evolving and conserved target antigens. J Immunol. 1981 Mar;126(3):969–974. [PubMed] [Google Scholar]
- Collins J. L., Patek P. Q., Cohn M. Tumorigenicity and lysis by natural killers. J Exp Med. 1981 Jan 1;153(1):89–106. doi: 10.1084/jem.153.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cudkowicz G., Hochman P. S. Do natural killer cells engage in regulated reactions against self to ensure homeostasis? Immunol Rev. 1979;44:13–41. doi: 10.1111/j.1600-065x.1979.tb00266.x. [DOI] [PubMed] [Google Scholar]
- Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981 Aug;127(2):590–595. [PubMed] [Google Scholar]
- Dennert G., Yogeeswaran G., Yamagata S. Cloned cell lines with natural killer activity. Specificity, function, and cell surface markers. J Exp Med. 1981 Mar 1;153(3):545–556. doi: 10.1084/jem.153.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
- Fast L. D., Hansen J. A., Newman W. Evidence for T cell nature and heterogeneity within natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) effectors: a comparison with cytolytic T lymphocytes (CTL). J Immunol. 1981 Aug;127(2):448–452. [PubMed] [Google Scholar]
- Haller O., Hansson M., Kiessling R., Wigzell H. Role of non-conventional natural killer cells in resistance against syngeneic tumour cells in vivo. Nature. 1977 Dec 15;270(5638):609–611. doi: 10.1038/270609a0. [DOI] [PubMed] [Google Scholar]
- Hansson M., Kiessling R., Andersson B. Human fetal thymus and bone marrow contain target cells for natural killer cells. Eur J Immunol. 1981 Jan;11(1):8–12. doi: 10.1002/eji.1830110103. [DOI] [PubMed] [Google Scholar]
- Herberman R. B., Nunn M. E., Lavrin D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975 Aug 15;16(2):216–229. doi: 10.1002/ijc.2910160204. [DOI] [PubMed] [Google Scholar]
- Herberman R. B., Nunn M. E., Lavrin D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975 Aug 15;16(2):216–229. doi: 10.1002/ijc.2910160204. [DOI] [PubMed] [Google Scholar]
- Hollander N., Pillemer E., Weissman I. L. Blocking effect of lyt-2 antibodies on T cell functions. J Exp Med. 1980 Sep 1;152(3):674–687. doi: 10.1084/jem.152.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamoun M., Martin P. J., Hansen J. A., Brown M. A., Siadak A. W., Nowinski R. C. Identification of a human T lymphocyte surface protein associated with the E-rosette receptor. J Exp Med. 1981 Jan 1;153(1):207–212. doi: 10.1084/jem.153.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kasai M., Leclerc J. C., McVay-Boudreau L., Shen F. W., Cantor H. Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo. J Exp Med. 1979 May 1;149(5):1260–1264. doi: 10.1084/jem.149.5.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
- Lindahl K. F., Lemke H. Inhibition of killer-target cell interaction by monoclonal anti-H-2 antibodies. Eur J Immunol. 1979 Jul;9(7):526–536. doi: 10.1002/eji.1830090708. [DOI] [PubMed] [Google Scholar]
- O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
- Phillips W. H., Ortaldo J. R., Herberman R. B. Selective depletion of human natural killer cells on monolayers of target cells. J Immunol. 1980 Nov;125(5):2322–2327. [PubMed] [Google Scholar]
- Seaman W. E., Talal N., Herzenberg L. A., Herzenberg L. A., Ledbetter J. A. Surface antigens on mouse natural killer cells: use of monoclonal antibodies to inhibit or to enrich cytotoxic activity. J Immunol. 1981 Sep;127(3):982–986. [PubMed] [Google Scholar]
- Shinohara N., Sachs D. H. Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus. J Exp Med. 1979 Sep 19;150(3):432–444. doi: 10.1084/jem.150.3.432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stern P., Gidlund M., Orn A., Wigzell H. Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC. Nature. 1980 May 29;285(5763):341–342. doi: 10.1038/285341a0. [DOI] [PubMed] [Google Scholar]
- Trucco M. M., Garotta G., Stocker J. W., Ceppellini R. Murine monoclonal antibodies against HLA structures. Immunol Rev. 1979;47:219–252. doi: 10.1111/j.1600-065x.1979.tb00295.x. [DOI] [PubMed] [Google Scholar]
- Welsh R. M., Jr, Zinkernagel R. M. Heterospecific cytotoxic cell activity induced during the first three days of acute lymphocytic choriomeningitis virus infection in mice. Nature. 1977 Aug 18;268(5621):646–648. doi: 10.1038/268646a0. [DOI] [PubMed] [Google Scholar]

