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. 1991 Jun 1;173(6):1451–1461. doi: 10.1084/jem.173.6.1451

Evidence for the involvement of CD56 molecules in alloantigen-specific recognition by human natural killer cells

PMCID: PMC2190827  PMID: 1709676

Abstract

In recent reports we have described the generation of natural killer (NK) lines devoid of CD3/TCR structures but with apparent specificity for allogeneic target cells. Using one such NK line as an immunogen, we now report the generation of two monoclonal antibodies (mAbs), designated 2-13 and 5-38, which bind selectively to the majority of CD3- , CD16+, CD56+ lymphocytes and inhibit the lysis of specific allogeneic target cells by a panel of alloreactive NK lines. By contrast, these mAbs had no effect on classical NK cell mediated lysis of K562 cells or major histocompatibility-restricted T cell-mediated cytolysis. Immunoprecipitation of radiolabeled NK lines followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the target molecules of both mAbs have a molecular mass of approximately 180 kD. Leu 19, a well-described anti-CD56 mAb, precipitated a 180 kD protein from NK cells, and the binding of Leu 19 to NK cells was blocked by pretreatment with both 2-13 and 5-38. However, in contrast to these mAbs, Leu 19 had no effect on the cytolytic activity of allospecific NK cells. Sequential immunoprecipitation analysis revealed that all three mAbs recognized distinct molecular species of CD56. We interpret these findings as indicating that multiple isoforms of CD56 are differentially expressed on NK lines and play critical roles in the recognition/interaction of these cells with their specific allogeneic targets.

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Selected References

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  1. Anegón I., Cuturi M. C., Trinchieri G., Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 1988 Feb 1;167(2):452–472. doi: 10.1084/jem.167.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barton C. H., Dickson G., Gower H. J., Rowett L. H., Putt W., Elsom V., Moore S. E., Goridis C., Walsh F. S. Complete sequence and in vitro expression of a tissue-specific phosphatidylinositol-linked N-CAM isoform from skeletal muscle. Development. 1988 Sep;104(1):165–173. doi: 10.1242/dev.104.1.165. [DOI] [PubMed] [Google Scholar]
  3. Bender J. R., Pardi R., Engleman E. T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6949–6953. doi: 10.1073/pnas.87.18.6949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bordignon C., Daley J. P., Nakamura I. Hematopoietic histoincompatibility reactions by NK cells in vitro: model for genetic resistance to marrow grafts. Science. 1985 Dec 20;230(4732):1398–1401. doi: 10.1126/science.3906897. [DOI] [PubMed] [Google Scholar]
  5. Ciccone E., Viale O., Pende D., Malnati M., Biassoni R., Melioli G., Moretta A., Long E. O., Moretta L. Specific lysis of allogeneic cells after activation of CD3- lymphocytes in mixed lymphocyte culture. J Exp Med. 1988 Dec 1;168(6):2403–2408. doi: 10.1084/jem.168.6.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
  7. Cudkowicz G., Nakamura I. Genetics of the murine hemopoietic-histocompatibility system: an overview. Transplant Proc. 1983 Dec;15(4):2058–2063. [PubMed] [Google Scholar]
  8. Cunningham B. A., Hemperly J. J., Murray B. A., Prediger E. A., Brackenbury R., Edelman G. M. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science. 1987 May 15;236(4803):799–806. doi: 10.1126/science.3576199. [DOI] [PubMed] [Google Scholar]
  9. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Irahara M., Kamada M., Mori T., Sudo T., Mori T. Inhibitory effects of tunicamycin on the mixed lymphocyte reaction and mitogen-induced lymphocyte blastogenesis. Immunobiology. 1987 Mar;174(2):190–199. doi: 10.1016/S0171-2985(87)80038-4. [DOI] [PubMed] [Google Scholar]
  11. Katz J. D., Ohnishi K., Lebow L. T., Bonavida B. The SJL/J T cell response to both spontaneous and transplantable syngeneic reticulum cell sarcoma is mediated predominantly by the V beta 17a+ T cell clonotype. J Exp Med. 1988 Nov 1;168(5):1553–1562. doi: 10.1084/jem.168.5.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koide J., Rivas A., Engleman E. G. Natural killer (NK)-like cytotoxic activity of allospecific T cell receptor-gamma,delta+ T cell clones. Distinct receptor-ligand interactions mediate NK-like and allospecific cytotoxicity. J Immunol. 1989 Jun 15;142(12):4161–4168. [PubMed] [Google Scholar]
  13. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  14. Lanier L. L., Ruitenberg J. J., Phillips J. H. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol. 1988 Nov 15;141(10):3478–3485. [PubMed] [Google Scholar]
  15. Lanier L. L., Testi R., Bindl J., Phillips J. H. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989 Jun 1;169(6):2233–2238. doi: 10.1084/jem.169.6.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McClain D. A., Edelman G. M. A neural cell adhesion molecule from human brain. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6380–6384. doi: 10.1073/pnas.79.20.6380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moretta A., Tambussi G., Bottino C., Tripodi G., Merli A., Ciccone E., Pantaleo G., Moretta L. A novel surface antigen expressed by a subset of human CD3- CD16+ natural killer cells. Role in cell activation and regulation of cytolytic function. J Exp Med. 1990 Mar 1;171(3):695–714. doi: 10.1084/jem.171.3.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nitta T., Yagita H., Sato K., Okumura K. Involvement of CD56 (NKH-1/Leu-19 antigen) as an adhesion molecule in natural killer-target cell interaction. J Exp Med. 1989 Nov 1;170(5):1757–1761. doi: 10.1084/jem.170.5.1757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
  20. 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]
  21. Roder J. C., Ahrlund-Richter L., Jondal M. Target-effector interaction in the human and murine natural killer system: specificity and xenogeneic reactivity of the solubilized natural killer-target structure complex and its loss in a somatic cell hybrid. J Exp Med. 1979 Sep 19;150(3):471–481. doi: 10.1084/jem.150.3.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sasaki D. T., Dumas S. E., Engleman E. G. Discrimination of viable and non-viable cells using propidium iodide in two color immunofluorescence. Cytometry. 1987 Jul;8(4):413–420. doi: 10.1002/cyto.990080411. [DOI] [PubMed] [Google Scholar]
  23. Sentman C. L., Hackett J., Jr, Kumar V., Bennett M. Identification of a subset of murine natural killer cells that mediates rejection of Hh-1d but not Hh-1b bone marrow grafts. J Exp Med. 1989 Jul 1;170(1):191–202. doi: 10.1084/jem.170.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stein B. S., Engleman E. G. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J Biol Chem. 1990 Feb 15;265(5):2640–2649. [PubMed] [Google Scholar]
  25. Suzuki N., Bianchi E., Bass H., Suzuki T., Bender J., Pardi R., Brenner C. A., Larrick J. W., Engleman E. G. Natural killer lines and clones with apparent antigen specificity. J Exp Med. 1990 Aug 1;172(2):457–462. doi: 10.1084/jem.172.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takada S., Engleman E. G. Evidence for an association between CD8 molecules and the T cell receptor complex on cytotoxic T cells. J Immunol. 1987 Nov 15;139(10):3231–3235. [PubMed] [Google Scholar]
  27. Trinchieri G., Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed] [Google Scholar]
  28. van de Griend R. J., Bolhuis R. L., Stoter G., Roozemond R. C. Regulation of cytolytic activity in CD3- and CD3+ killer cell clones by monoclonal antibodies (anti-CD16, anti-CD2, anti-CD3) depends on subclass specificity of target cell IgG-FcR. J Immunol. 1987 May 15;138(10):3137–3144. [PubMed] [Google Scholar]

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