Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 Sep 1;178(3):1121–1126. doi: 10.1084/jem.178.3.1121

A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity

PMCID: PMC2191151  PMID: 7688788

Abstract

Human lymphocytes with natural killer (NK) activity, including most activated gamma/delta+ T lymphocytes, recognize and lyse tumor target cells without requiring recognition of major histocompatibility complex antigen. However, unlike gamma/delta+ T lymphocytes, NK cells do not express CD3/T cell receptor (TCR) molecules, and the receptors involved in cell-mediated cytotoxicity are unknown. To further delineate circulating NK cells, we developed monoclonal antibodies (mAbs) against the human NK leukemia YT2C2. We report the isolation of a mAb termed BY55, recognizing at the cell surface a novel 80-kD protein with restricted expression. In addition to the immunizing cell line, this mAb binds to circulating NK cells, gamma/delta+ cells, and a minor subset of alpha/beta+ T lymphocytes. Expression of the BY55 mAb- reactive epitope/molecule is regulated by activation, as short-term culture of peripheral blood lymphocytes (PBL) with phorbol ester induced its downmodulation. Furthermore, BY55 mAb reactivity was found neither with the NK nor with the TCR alpha/beta+ gamma/delta+ clones tested. Biochemical studies as well as phenotypic analysis revealed that this structure is different from all previously identified molecules on the lymphocyte cell surface. Interestingly, we found that BY55+ cells exert most NK activity obtained with fresh circulating lymphocytes. We report that within fresh E rosette-positive PBL only a subset of the CD16+, CD56+, and CD57+ cells coexpressed BY55 molecule, indicating that BY55 mAb defines a unique subset mediating NK activity of circulating PBL.

Full Text

The Full Text of this article is available as a PDF (634.9 KB).

Selected References

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

  1. Anderson P., Caligiuri M., O'Brien C., Manley T., Ritz J., Schlossman S. F. Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2274–2278. doi: 10.1073/pnas.87.6.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aramburu J., Balboa M. A., Izquierdo M., López-Botet M. A novel functional cell surface dimer (Kp43) expressed by natural killer cells and gamma/delta TCR+ T lymphocytes. II. Modulation of natural killer cytotoxicity by anti-Kp43 monoclonal antibody. J Immunol. 1991 Jul 15;147(2):714–721. [PubMed] [Google Scholar]
  3. Aramburu J., Balboa M. A., Ramírez A., Silva A., Acevedo A., Sánchez-Madrid F., De Landázuri M. O., López-Botet M. A novel functional cell surface dimer (Kp43) expressed by natural killer cells and T cell receptor-gamma/delta+ T lymphocytes. I. Inhibition of the IL-2-dependent proliferation by anti-Kp43 monoclonal antibody. J Immunol. 1990 Apr 15;144(8):3238–3247. [PubMed] [Google Scholar]
  4. Bensussan A., Lagabrielle J. F., Degos L. TCR gamma delta bearing lymphocyte clones with lymphokine-activated killer activity against autologous leukemic cells. Blood. 1989 Jun;73(8):2077–2080. [PubMed] [Google Scholar]
  5. Bensussan A., Tourvieille B., Chen L. K., Dausset J., Sasportes M. Phorbol ester induces a differential effect on the effector function of human allospecific cytotoxic T lymphocyte and natural killer clones. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6642–6646. doi: 10.1073/pnas.82.19.6642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bougeret C., Mansur I. G., Dastot H., Schmid M., Mahouy G., Bensussan A., Boumsell L. Increased surface expression of a newly identified 150-kDa dimer early after human T lymphocyte activation. J Immunol. 1992 Jan 15;148(2):318–323. [PubMed] [Google Scholar]
  7. Dastot H., Schmid M., Gontier C., Amiot M., Mathieu-Mahul D., Bensussan A., Boumsell L. Correlation between T cell receptor gamma delta isotypic forms and cytotoxic activity: analysis with human T cell clones and lines. Cell Immunol. 1990 Feb;125(2):315–325. doi: 10.1016/0008-8749(90)90087-8. [DOI] [PubMed] [Google Scholar]
  8. David V., Bachelez H., Leca G., Degos L., Boumsell L., Bensussan A. Identification of a novel 110-kilodalton structure expressed on a subset of T cell receptor-gamma delta-bearing cloned lymphocytes. J Immunol. 1990 Jan 1;144(1):1–6. [PubMed] [Google Scholar]
  9. David V., Bourge J. F., Guglielmi P., Mathieu-Mahul D., Degos L., Bensussan A. Human T cell clones use a CD3-associated surface antigen recognition structure to exhibit both NK-like and allogeneic cytotoxic reactivity. J Immunol. 1987 May 1;138(9):2831–2836. [PubMed] [Google Scholar]
  10. David V., Leca G., Vilmer E., Guglielmi P., Chouaib S., Kanellopoulos J., Sigaux F., Bensussan A. Expression of the T cell gamma gene by a functionally defined human T cell clone. Characterization at DNA, RNA, and cell membrane level. Scand J Immunol. 1988 Apr;27(4):473–483. doi: 10.1111/j.1365-3083.1988.tb02373.x. [DOI] [PubMed] [Google Scholar]
  11. Fleit H. B., Wright S. D., Unkeless J. C. Human neutrophil Fc gamma receptor distribution and structure. Proc Natl Acad Sci U S A. 1982 May;79(10):3275–3279. doi: 10.1073/pnas.79.10.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Lanier L. L., Chang C., Azuma M., Ruitenberg J. J., Hemperly J. J., Phillips J. H. Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol. 1991 Jun 15;146(12):4421–4426. [PubMed] [Google Scholar]
  14. Lanier L. L., Cwirla S., Federspiel N., Phillips J. H. Human natural killer cells isolated from peripheral blood do not rearrange T cell antigen receptor beta chain genes. J Exp Med. 1986 Jan 1;163(1):209–214. doi: 10.1084/jem.163.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  17. 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]
  18. Lanier L. L., Yu G., Phillips J. H. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989 Dec 14;342(6251):803–805. doi: 10.1038/342803a0. [DOI] [PubMed] [Google Scholar]
  19. Lebow L. T., Bonavida B. Purification and characterization of cytolytic and noncytolytic human natural killer cell subsets. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6063–6067. doi: 10.1073/pnas.87.16.6063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moingeon P., Jitsukawa S., Faure F., Troalen F., Triebel F., Graziani M., Forestier F., Bellet D., Bohuon C., Hercend T. A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. Nature. 1987 Feb 19;325(6106):723–726. doi: 10.1038/325723a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Nagler A., Lanier L. L., Cwirla S., Phillips J. H. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989 Nov 15;143(10):3183–3191. [PubMed] [Google Scholar]
  23. Nakamura Y., Inamoto T., Sugie K., Masutani H., Shindo T., Tagaya Y., Yamauchi A., Ozawa K., Yodoi J. Mitogenicity and down-regulation of high-affinity interleukin 2 receptor by YTA-1 and YTA-2, monoclonal antibodies that recognize 75-kDa molecules on human large granular lymphocytes. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1318–1322. doi: 10.1073/pnas.86.4.1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perussia B., Acuto O., Terhorst C., Faust J., Lazarus R., Fanning V., Trinchieri G. 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. 1983 May;130(5):2142–2148. [PubMed] [Google Scholar]
  25. Ritz J., Campen T. J., Schmidt R. E., Royer H. D., Hercend T., Hussey R. E., Reinherz E. L. Analysis of T-cell receptor gene rearrangement and expression in human natural killer clones. Science. 1985 Jun 28;228(4707):1540–1543. doi: 10.1126/science.2409597. [DOI] [PubMed] [Google Scholar]
  26. Ritz J., Schmidt R. E., Michon J., Hercend T., Schlossman S. F. Characterization of functional surface structures on human natural killer cells. Adv Immunol. 1988;42:181–211. doi: 10.1016/s0065-2776(08)60845-7. [DOI] [PubMed] [Google Scholar]
  27. Takeshita T., Goto Y., Tada K., Nagata K., Asao H., Sugamura K. Monoclonal antibody defining a molecule possibly identical to the p75 subunit of interleukin 2 receptor. J Exp Med. 1989 Apr 1;169(4):1323–1332. doi: 10.1084/jem.169.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Timonen T., Ortaldo J. R., Herberman R. B. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981 Mar 1;153(3):569–582. doi: 10.1084/jem.153.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tschopp J., Nabholz M. Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol. 1990;8:279–302. doi: 10.1146/annurev.iy.08.040190.001431. [DOI] [PubMed] [Google Scholar]
  31. Werfel T., Witter W., Götze O. CD11b and CD11c antigens are rapidly increased on human natural killer cells upon activation. J Immunol. 1991 Oct 1;147(7):2423–2427. [PubMed] [Google Scholar]

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

RESOURCES