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Functional surface structures on human natural killer cells

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Summary

This manuscript reviews recent studies on the characterization of functional surface antigens on human NK cells. A series of cloned NK cell lines has been utilized for examination of these structures. These clones provide a relatively large number of cells with a stable phenotype and consistent specific cytotoxicity, which reflect the diversity of uncultured NK cells in normal peripheral blood. Almost all clones express the T11 antigen, some have a mature T-cell phenotype (T3+, T11+), and only one (JT1) does not reveal any T-cell antigen at all (T3−, T11+). Using NK clones to generate monoclonal antibodies specific for NK-associated antigens, two structures have been identified, NKH1 and NKH2. NKH1 appears to be exclusively expressed on large granular lymphocytes (LGL) of peripheral blood and was found to be a pan-NK cell antigen. NKH2 is also expressed primarily by LGL, but NKH2-positive LGL do not display a high level of NK activity. Another surface structure that has been found to play an important role in NK cell function is the T11 antigen/E rosette receptor complex, which is expressed in 80% of peripheral blood NK cells. The T11 antigen complex has been described as possessing the T111, T112, and T113 antigens and is an important alternate pathway for antigen-independent T-cell activation. Using anti-T112 and anti-T113 monoclonal antibodies, IL-2 receptor expression could be induced on various NK clones if they expressed the correct T11 antigenic epitope. As anti-T112/3 antibodies had a direct proliferative effect on NK cells with mature T-cell phenotype (T3+), it is proposed that the production of IL-2 by NK clones is largely dependent on the T-cell phenotype of NK cells. All NK clones expressed IL-2 receptor at low density and therefore needed a ten fold higher concentration for maximal proliferation than T-cell clones.

For some T-cell-like NK clones, the T3 antigen complex and a T-cell receptor-like structure, NKTa or NKTb, have been shown to define the target cell specificity. The activation antigen, TNKTAR, was characterized as the recognition structure on the target cell for these NK cells. For both T3− and T3+ NK clones, the LFA-1 antigen has been shown to play an important role in effector/target cell interaction. As previously described for CTL, the LFA-1 molecule is involved in NK cytotoxicity as a nonspecific adhesion-strengthening molecule at the effector cell level.

In summary, NK cells have been found to have a number of unique surface antigens such as NKH1 and NKH2, which can be used to identify and characterize NK cells in vivo. In addition, analysis of surface antigens on NK cells has identified a number of functional structures, such as T11, T3, NKTa and LFA-1, which are shared by T-cells and which function in a fashion similar to both types of cells. Taken together, this analysis therefore indicates that NK cells have a strong functional relationship with T-cells and supports the conclusion that these cells are derived from the T-cell lineage.

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Abbreviations

CTL:

cytotoxic T cell

IL-2:

interleukin 2

LCM:

lymphocyte conditioned media

LFA-1:

leukocyte function antigen-1

LGL:

large granular lymphocytes

NK:

natural killer

PBMC:

peripheral blood mononuclear cells

PHA:

phytohemagglutinin

PMA:

phorbol myristate acetate

References

  1. Abo T, Balch CM (1981) A differentiation antigen of human NK and K-cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029

    Google Scholar 

  2. Abo T, Cooper MD, Balch CM (1982) Postnatal expansion of the natural killer and killer cell population in humans identified by the monoclonal HNK-1 antibody. J Exp Med 155:321–326

    Google Scholar 

  3. Abruzzo LV, Rowley DA (1983) Homeostatis of the antibody response: immunoregulation by NK cells. Science 222:581–583

    Google Scholar 

  4. Allavena P, Ortaldo JR (1984) Characteristics of human NK clones: target specificity and phenotype. J Immunol 132:2363–2369

    Google Scholar 

  5. Carpen O, Virtanen I, Saksela E (1982) Ultrastructure of the human natural killer cells: nature of the cytolytic contacts in relation to cellular secretion. J Immunol 128:2691–2697

    Google Scholar 

  6. Fast LD, Hansen JA, Newman W (1981) Evidence for T-cell nature and heterogeneity within natural killer (NK) and antibody dependent cellular cytotoxicity (ADCC) effectors: a comparison with cytotoxic T lymphocytes (CTL). J Immunol 127:448–452

    Google Scholar 

  7. Fox DA, Hussey RE, Fitzgerald KA, Bensussan A, Daley JF, Schlossman SF, Reinherz EL (1985) Activation of human thymocytes via the 50 KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptor on both T3+ and T3− populations. J Immunol 134:330–335

    Google Scholar 

  8. Griffin JD, Hercend T, Beveridge R, Schlossman SF (1983) Characterization of an antigen expressed by human natural killer cells. J Immunol 130:2947–2951

    Google Scholar 

  9. Hansson M, Beran M, Anderson B, Kiessling R (1983) Inhibition of in vitro granulopoiesis by autologous allogeneic human cells. J Immunol 129:126–131

    Google Scholar 

  10. Haynes BF, Hemler ME, Mann DL, Eisenbarth GW, Schelhamer J, Mostowski HS, Thomas CA, Strominger JL, Fauci AS (1981) Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. J Immunol 126:1409–1414

    Google Scholar 

  11. Herberman RB, Ortaldo JR (1981) Natural killer cells: their role in defenses against disease. Science 214:25–30

    Google Scholar 

  12. Hercend T, Meuer SC, Reinherz EL, Schlossman SF, Ritz J (1982) Generation of a cloned NK cell line derived from the “null cell” fraction of human peripheral blood. J Immunol 129:1299–1305

    Google Scholar 

  13. Hercend T, Reinherz EL, Meuer SC, Schlossman SF, Ritz J (1983) Phenotypic and functional heterogeneity of human cloned natural killer cell lines. Nature (Lond) 301:158–160

    Google Scholar 

  14. Hercend T, Meuer SC, Brennan A, Edson MA, Acuto O, Reinherz EL, Schlossman SF, Ritz J (1983) Identification of a clonally restricted 90 KD heterodimer on two human cloned natural killer cell lines: its role in cytotoxic effector function. J Exp Med 158:1547–1560

    Google Scholar 

  15. Hercend T, Meuer SC, Brennan A, Edson MA, Acuto O, Reinherz EL, Schlossman SF, Ritz J (1984) Natural killer-like function of activated T lymphocytes: differential blocking effects of monoclonal antibodies specific for a 90 KD clonotypic structure. Cell Immunol 86:381–392

    Google Scholar 

  16. Hercend T, Schmidt RE, Brennan A, Edson MA, Reinherz EL, Schlossman SF, Ritz J (1984) Identification of a 140 KD activation antigen as a target structure for a series of human cloned NK cell lines. Eur J Immunol 14:844–852

    Google Scholar 

  17. Hercend T, Griffin JD, Bensussan A, Schmidt RE, Murray C, Edson MA, Brennan A, Daley JF, Schlossman SF, Ritz J (1985) Generation of monoclonal antibodies to a human natural killer clones: characterization of two NK associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 75:932–943

    Google Scholar 

  18. Herrmann F, Cannistra SA, Levine H, Griffin JD (1985) Expression of interleukin 2 receptor and binding of interleukin 2 by gamma interferon induced human leukemic and normal monocytic cells. J Exp Med (in press)

  19. Hildreth JEK, Gotch FM, Hildreth PDK, McMichael AJ (1983) A human lymphocyte associated antigen involved in cell mediated lympholysis. Eur J Immunol 13:202–208

    Google Scholar 

  20. Howard FD, Ledbetter JA, Wong Y, Bieber CP, Stinson EB, Herzenberg LA (1981) A human T lymphocyte differentiation marker defined by monoclonal antibodies that block E rosette formation. J Immunol 126:2117–2122

    Google Scholar 

  21. Kohl S, Springer TA, Schmalstieg FC, Loo LS, Anderson DC (1984) Defective natural killer cell cytotoxicity in patients with LFA-1/OKM1 deficiency. J Immunol 131:2972–2976

    Google Scholar 

  22. MacDermott RP, Schmidt RE, Caulfield JP, Hein A, Bartley GT, Ritz J, Schlossman SF, Austen KF, Stevens RL (1985) Proteoglycans in cell mediated cytotoxicity: identification, localization and exocytosis of a chondroitin sulfate proteoglycan from human cloned natural killer cells during cytotoxicity. J Exp Med (in press)

  23. Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL (1983) Clonotypic structures involved in antigen specific human T-cell function. J Exp Med 157:705–719

    Google Scholar 

  24. Meuer SC, Hussey RE, Fabbi M, Fox D, Acuto O, Fitzgerald KA, Hodgdon JC, Protentis JP, Schlossman SF, Reinherz EL (1984) An alternative pathway of T-cell activation: a functional role for the 50 KD T11 sheep erythrocyte receptor protein. Cell 36:897–906

    Google Scholar 

  25. Moingeon P, Nowill A, Courtois G, Azzarone B, Motte P, Ythier A, Bohuon C, Hercend T (1985) A target structure for a series of human cloned natural killer cell lines is recognized by both anti-TNKTAR and 4F2 monoclonal antibodies. J Immunol 134:2930–2934

    Google Scholar 

  26. Ortaldo JR, Sharrow SO, Timonen T, Herberman RB (1981) Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol 127:2401–2409

    Google Scholar 

  27. Ortaldo JR, Mason AT, Gerard JP, Henderson LF, Farrar W, Hopkins RF, Herberman FB, Rabin H (1984) Effects of natural and recombinant IL-2 on regulation of IFN production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol 133:779–783

    Google Scholar 

  28. Perussia B, Starr S, Abraham S, Fanning V, Trinchieri G (1983) 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 130:2133–2141

    Google Scholar 

  29. Perussia B, Oreste A, Terhorst C, Faust J, Lazarus R, Fanning V, Trinchieri G (1983) Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J Immunol 130:2142–2148

    Google Scholar 

  30. Perussia B, Fanning V, Trinchieri G (1983) A human NK and K-cell subset shares with cytotoxic T-cell expression of the antigen recognized by antibody OKT8. J Immunol 131:223–231

    Google Scholar 

  31. Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1979) A monoclonal antibody with selective reactivity with functionally mature thymocytes and all peripheral human T-cells. J Immunol 123:1312–1317

    Google Scholar 

  32. Reinherz EL, Schlossman SF (1980) The differentiation and function of human T lymphocytes: a review. Cell 19:821–827

    Google Scholar 

  33. Ritz J, Campen TC, Schmidt RE, Royer HD, Hercend T, Hussey RE, Reinherz EL (1985) Analysis of T-cell receptor rearrangement and expression in human natural killer (NK) clones. Science 228:1540–1543

    Google Scholar 

  34. Saksela E, Timonen T, Rauki A, Hayry P (1979) Fractionation, morphological and functional characterization of effector cell responsible for human natural killer activity to fetal fibroblasts and cell line targets. Immunol Rev 44:71–123

    Google Scholar 

  35. Schmidt RE, Hercend T, Fox DA, Bensussan A, Bartley G, Daley JF, Schlossman SF, Reinherz EL, Ritz J (1985) The role of interleukin 2 and T11 E rosette antigen in activation and proliferation of human NK clones. J Immunol 135:672–678

    Google Scholar 

  36. Schmidt RE, Bartley G, Levine H, Schlossman SF, Ritz J (1985) Functional characterization of LFA-1 antigens in the interaction of human NK clones and target cells. J Immunol 135:1020–1025

    Google Scholar 

  37. Schmidt RE, Bartley G, Hercend T, Schlossman SF, Ritz J (1985) NK associated and LFA-1 antigens: phenotypic and functional studies utilizing human NK clones. In: Reinherz EL, Haynes BF, Nadler LM, Bernstein ID (eds) Leucocyte Typing II. Springer, New York (in press)

    Google Scholar 

  38. Schmidt RE, MacDermott RP, Bartley G, Bertovich M, Austen KF, Schlossman SF, Stevens RL, Ritz J (1985) Specific involvement of chrondroitin sulfate proteoglycans in cytotoxicity of human natural killer cells. Nature (in press)

  39. Springer T, Davignon D, Ho M, Kurzinger K, Martz E, Sanchez-Madrid F (1982) LFA-1 and Lyt2,3 molecules associated with T lymphocyte mediated killing, and Mac-1, an LFA-1 homologous associated with complement receptor function. Immunol Rev 68:171–192

    Google Scholar 

  40. Timonen T, Saksela E (1980) Isolation of human NK cells by density gradient centrifugation. J Immunol Meth 36:285–287

    Google Scholar 

  41. Timonen T, Ortaldo JR, Herberman RB (1981) Characteristics of human large granular lymphocytes and relationship to natural killer and K-cells. J Exp Med 153:569–582

    Google Scholar 

  42. Trinchieri G, Santoli D (1978) Anti-viral activity induced by culturing lymphocytes with tumor derived or virus transformed cells: enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med 147:1314–1333

    Google Scholar 

  43. Trinchieri G, Santoli D, Dee RR, Knowles BB (1978) Antiviral activity induced by culturing lymphocytes with tumor derived or virus transformed cells: identification of the antiviral activity as interferon and characterization of the human effector lymphocyte subpopulation. J Exp Med 147:1299–1313

    Google Scholar 

  44. Trinchieri G, Matrumoto-Hobayashi M, Clark SC, Seehra J, London L, Perussia B (1984) Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med 160:1147–1162

    Google Scholar 

  45. Trinchieri G, Perussia B (1984) Human natural killer cells: Biologic and pathologic aspects. Lab Invest 50:498–513

    Google Scholar 

  46. Uchiyama T, Broder S, Waldmann TA (1981) A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T-cells. I. Production of anti-Tac antibody and distribution of Tac (+) cells. J Immunol 126:1393–1397

    Google Scholar 

  47. Waldmann TA, Goldman CK, Robb RJ, Depper JM, Leonard WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WC (1984) Expression of interleukin 2 receptor on activated human B-cells. J Exp Med 160:1450–1466

    Google Scholar 

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Authors and Affiliations

  1. Division of Tumor Immunology, Dana-Farber Cancer Institute and the Department of Medicine, Harvard Medical School, Boston, USA

    R. E. Schmidt, T. Hercend, S. F. Schlossman & J. Ritz

  2. Medizinische Universitätsklinik, Sigmund-Freud-Strasse 25, D-5300, Bonn 1

    R. E. Schmidt

Authors
  1. R. E. Schmidt
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  2. T. Hercend
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  3. S. F. Schlossman
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  4. J. Ritz
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Dedicated to Professor Hans J. Dengler on the occasion of his 60th birthday

This work was supported by NIH grant CA 34183

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Schmidt, R.E., Hercend, T., Schlossman, S.F. et al. Functional surface structures on human natural killer cells. Klin Wochenschr 63, 1189–1200 (1985). https://doi.org/10.1007/BF01733777

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  • DOI: https://doi.org/10.1007/BF01733777

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