Monoclonal Antibody Strategy and Techniques

  • Zelig Eshhar


The novel approach of immortalizing specific antibody-forming cells by their fusion with myeloma cells was first introduced by Köhler and Milstein1 in 1975. Since then it has been widely adopted as the method of choice for the preparation of monoclonal antibodies (MAbs) to a large spectrum of antigens, and today MAbs find application in almost all facets of the life sciences. The thousands of research articles published every year that report the use of MAb as the key reagent and the tens of biotechnology companies that are involved in MAb production exemplify only part of the revolutionary impact of monoclonal antibodies.


Spleen Cell Myeloma Cell Hybrid Cell Myeloma Cell Line Cloning Efficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Köhler, G., and Milstein, C., 1974, Continuous cultures of fused cells secreting antibody of predefined specificity, Nature 256:495–497.CrossRefGoogle Scholar
  2. 2.
    Nossal G. J. V., and Lederberg, J., 1958, Antibody production by single cells, Nature 181:1419–1421.PubMedCrossRefGoogle Scholar
  3. 3.
    Burnet, F. M., 1957, A modification of Jerne’s theory of antibody production using the concept of clonal selection, Austr. J. Sci. 20:67–69.Google Scholar
  4. 4.
    Lane, D., and Koprowski, H., 1982, Molecular recognition and the future of monoclonal antibodies, Nature 296:200–202.PubMedCrossRefGoogle Scholar
  5. 5.
    Pillemer, E., and Weissman, I. L., 1981, A monoclonal antibody that detects a Vk-TEPC-15 idiotypic determinant cross reactive with a Thy-1 determinant, J. Exp. Med. 153:1068–1079.PubMedCrossRefGoogle Scholar
  6. 6.
    Galfrè, G., Howe, S., Milstein, C., Butcher, G. W., and Howard, J., 1977, Antibodies to major histocompatibility antigens produced by hybrid cell lines, Nature 266:550–552.PubMedCrossRefGoogle Scholar
  7. 7.
    Littlefield, J. W., 1964, Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants, Science 145:709–710.PubMedCrossRefGoogle Scholar
  8. 8.
    Cotton, R. G. H., and Milstein, C., 1973, Fusion of two immunoglobulin-producing myeloma cells, Nature 244:42–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Kelly, T., Scharff, M. D., Cieplinski, W., Dharmgrongartama, B., Gefter, M. L., and Morrison, S. L., 1977, Regulation of immunoglobulin expression in mouse myeloma cells, Cold Spring Harbor Symp. Quant. Biol. 41:781–791.PubMedCrossRefGoogle Scholar
  10. 10.
    Parhami-Seren, B., Eshhar, Z., and Mozes, E., 1983, Fine specificity and idiotypic expression of monoclonal antibodies directed against (T,G)-A-L and its ordered analog (T,T,G,G)-A-L, Immunology 49:6–16.Google Scholar
  11. 11.
    Bahr, G. M., Eshhar, Z., Ben Itzhak, R., Modabar, F. Z., Arnon, R., Sela, M., and Chedid, L., 1983, Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: Characterization and specificity, J. Mol. Immunol. 20:745–752.CrossRefGoogle Scholar
  12. 12.
    Novick, D., Eshhar, Z., and Rubinstein, M., 1982, Monoclonal antibodies to human interferon and their use for affinity chromatography, J. Immunol. 129:2244–2248.PubMedGoogle Scholar
  13. 13.
    Novick, D., Eshhar, Z., Gigi, O., Marks, Z., Revel, M., and Rubinstein, M., 1983, Affinity chromatography of human fibroblast interferon (IFN-β1), by monoclonal antibody columns, J. Gen. Virol. 64:905–910.PubMedCrossRefGoogle Scholar
  14. 14.
    Novick, D., Eshhar, Z., Fischer, D. G., Friedlander, J., and Rubinstein, M., 1983, Monoclonal antibody to human interferon-γ: Production, affinity purification and radioimmunoassay, EMBO J. 2:1527–1530.PubMedGoogle Scholar
  15. 15.
    Moshly-Rosen, D., Fuchs, S., and Eshhar, Z., 1979, Monoclonal antibodies against defined determinants of acetylcholine receptor, FEBS Lett. 106:389–393.PubMedCrossRefGoogle Scholar
  16. 16.
    Schreiber, A. B., Lax, I., Yarden, Y., Eshhar, Z., and Schlessinger, J., 1981, Monoclonal antibodies against the receptor for epidermal growth factor induce early and delayed effects of epidermal growth factors, Proc. Natl. Acad. Sci. USA 78:7535–7540.PubMedCrossRefGoogle Scholar
  17. 17.
    Hadas, E., Hurwitz, E., and Eshhar, Z., 1984, Identification of a surface antigen common to murine lung and Lewis lung carcinoma by monoclonal antibodies, Int. J. Cancer 33:369–376.PubMedCrossRefGoogle Scholar
  18. 18.
    Melchers, F., Potter, M., and Warner, N. L. (eds.), 1978, Current Topics in Microbiology and Immunology, Volume 81, Springer-Verlag, New York.Google Scholar
  19. 19.
    Oi, V. T., and Herzenberg, L. A., 1980, Immunoglobulin-producing hybridoma cell lines, in: Selected Methods in Cellular Immunology (B. B. Mishell and S. M. Shiigii, eds.), Freeman, San Francisco, pp. 351–372.Google Scholar
  20. 20.
    Fazekas de St. Groth, S., and Scheidegger, D., 1980, Production of monoclonal antibodies: Strategy and tactics, J. Immunol. Meth. 35:1–21.CrossRefGoogle Scholar
  21. 21.
    Goding, J. W., 1980, Antibody production in hybridomas, J. Immunol. Meth. 39:289–308.CrossRefGoogle Scholar
  22. 22.
    Kennett, R. H., McKearn, T. J., and Bechtol, K. B. (eds.), 1980, Monoclonal Antibodies and Hybridomas: A New Dimension in Biological Analyses, Plenum Press, New York.Google Scholar
  23. 23.
    Hämmerling, G. J., Hammerling, U., and Kearney, J. F. (eds.), 1981, Monoclonal Antibodies and T Cell Hybridomas, Perspectives and Technical Advances, Elsevier/North-Holland, New York.Google Scholar
  24. 24.
    Galfrè, G., and Milstein, C., 1981, Preparation of monoclonal antibodies: Strategies and procedures, Meth. Enzymol. 73:3–46.PubMedCrossRefGoogle Scholar
  25. 25.
    Köhler, G., 1981, The technique of hybridoma production, in: Immunological Methods, Volume 2 (I. Lefkovits and B. Pernis, eds.), Academic Press, New York, pp. 285–298.Google Scholar
  26. 26.
    Goding, J. W., 1983, Monoclonal Antibodies: Principles and Practice, Academic Press, New York.Google Scholar
  27. 27.
    Weir, D. M. (ed.), 1978, Handbook of Experimental Immunology, 3rd ed. Academic Press, New York.Google Scholar
  28. 28.
    Williams, C. A., and Chase, M. W. (eds.), 1967–1976 Methods in Immunology and Immunochemistry, Volumes 1–5, Academic Press, New York.Google Scholar
  29. 29.
    Lefkovits, I., and Pernis, B. (eds.), 1981, Immunological Methods, Volumes 1 and 2, Academic Press, New York.Google Scholar
  30. 30.
    Langone, J., and Van Vunakis, H., 1980–1981, Immunological techniques (Parts A, B, and C), in: Methods in Enzymology, Volumes 70, 73, 74, Academic Press, New York.Google Scholar
  31. 31.
    Crumpton, M. J., 1974, Protein antigens: The molecular bases of antigenicity and immunogenicity, in: The Antigens, Volume 2 (M. Sela, ed.), Academic Press, New York, pp. 1–78.Google Scholar
  32. 32.
    Leder, P., 1982, The genetics of antibody diversity, Sci. Am. 246:102–113.PubMedCrossRefGoogle Scholar
  33. 33.
    Tonegawa, S., 1983, Somatic generation of antibody diversity, Nature 302:575–580.PubMedCrossRefGoogle Scholar
  34. 34.
    Honjo, T., 1983, Immunoglobulin genes, Annu. Rev. Immunol. 1:499–528.PubMedCrossRefGoogle Scholar
  35. 35.
    Coffman, R. L., and Cohn, M., 1977, The class of surface immunoglobulin on virgin and memory B lymphocytes, J. Immunol. 118:1806–1815.PubMedGoogle Scholar
  36. 36.
    Davis, M. M., Kim, S. K., and Hood, L., 1980, Immunoglobulin class switching developmentally regulated DNA rearrangement during differentiation, Cell 22:1–2.PubMedCrossRefGoogle Scholar
  37. 37.
    Marcu, K. B., Lang, R. B., Stanton, W. L., and Harris, L. J., 1982, A model for the molecular requirements of immunoglobulin heavy chain class switching, Nature 298:87–92.PubMedCrossRefGoogle Scholar
  38. 38.
    Gearhart, P., and Bogenhagen, D., 1983, Clusters of point mutations are found exclusively around rearranged antibody variable region genes, Proc. Natl. Acad. Sci USA 80:3439–3444.PubMedCrossRefGoogle Scholar
  39. 39.
    Levine, B. B., and Vaz, N. M., 1970, Effect of combination of inbred strain, antigen and antigen dose on immune responsiveness and reagin production in the mouse, Int. Arch. Allergy Appl. Immunol. 30:156–163.CrossRefGoogle Scholar
  40. 40.
    Tung, A. S., Chiorazzi, N., and Katz, D. H., 1978, Regulation of IgE antibody production by serum molecules. I. Serum from complete Freund’s adjuvant-immune donors suppresses irradiation-enhanced IgE production in low responder mouse strains, J. Immunol. 120:2050–2059.PubMedGoogle Scholar
  41. 41.
    Morisaki, I, Michalek, S. M., Harmon, C. C., Torii, S., and McGhee, J. R., 1983, Effective immunity to dental caries: Enhancement of salivary anti-Streptococcus mutans antibody responses with oral adjuvants, Infect. Immunol. 40:577–584.Google Scholar
  42. 42.
    Koshland, M. E., 1975, Structure and function of the J chain, Adv. Immunol. 20:41–69.CrossRefGoogle Scholar
  43. 43.
    Tomase, T. B., and Grey, H. M., 1972, Structure and function of immunoglobulin A, Prog. Allergy 16:81–185.CrossRefGoogle Scholar
  44. 44.
    Kuhn, L. C., and Kraehenbuhl, J.-P., 1981, The membrane receptor for polymeric immunoglobulin is structurally related to secretory component, J. Biol. Chem. 250:12490–12495.Google Scholar
  45. 45.
    Underdown, B. J., and Dorrington, K. J., 1974, Studies on the structural and conformational basis for the relative resistance of serum and secretory immunoglobulin-A to proteolysis, J. Immunol. 112:949–959.PubMedGoogle Scholar
  46. 46.
    Baniash, M., and Eshhar, Z., 1984, Inhibition of IgE binding to mast cells and basophils by monoclonal antibodies to murine IgE, Eur. J. Immunol. 14:799–807.CrossRefGoogle Scholar
  47. 47.
    Eshhar, Z., Gigi, O., Givol, D., and Ben-Neriah, Y., 1983, Monoclonal anti-VH antibodies recognize a common VH determinant expressed on immunoglobulin heavy chains from various species, Eur. J. Immunol. 13:533–540.PubMedCrossRefGoogle Scholar
  48. 48.
    Springer, T. A., 1981, Monoclonal antibody analysis of complex biological systems: Combination of cell hybridization and immunoadsorbents in a novel cascade procedure and its application to the macrophage cell surface, J. Biol. Chem. 256:3833–3840.PubMedGoogle Scholar
  49. 49.
    Springer, T. A., Kaufman, J. F., Siddoway, L. A., Mann, D. L., and Strominger, J. L., 1977, Purification of HL-A linked B lymphocyte alloantigens in immunologically active form by preparative sodium dodecyl sulfate-gel electrophoresis and studies on their subunit association, J. Biol. Chem. 252:6201–6207.PubMedGoogle Scholar
  50. 50.
    Boulard, C., and Lecroisey, A., 1982, Specific antisera produced by direct immunization with slices of Polyacrylamide gel containing small amounts of protein, J. Immunol. 50:221–226.Google Scholar
  51. 51.
    Erlanger, B. F., 1980, The preparation of antigenic hapten-carrier conjugates: A survey, Meth. Enzymol. 70:85–104.PubMedCrossRefGoogle Scholar
  52. 52.
    Bauminger, S., and Wilcheck, M., 1980, The use of carbodiimides in the preparation of immunizing conjugates, Meth. Enzymol. 70:151–159.PubMedCrossRefGoogle Scholar
  53. 53.
    Reichlin, M., 1980, Use of glutaraldehyde as a coupling agent for proteins and peptides, Meth. Enzymol. 70:159–165.PubMedCrossRefGoogle Scholar
  54. 54.
    Bazin, H., Backers, A., Deckers, C., and Moriame, M., 1973, Transplantable immunoglobulin-secreting tumors in rats. V. Monoclonal immunoglobulins secreted by 250 ileocecal immunocytomas in LOU/WJs rats, J. Natl. Cancer Inst. 51:1359–1361.PubMedGoogle Scholar
  55. 55.
    Anderson, J., and Melchers, F., 1978, The antibody repertoire of hybrid cell lines obtained by fusion of × 63-Ag8 myeloma cells with mitogen-activated B cell blasts, Curr. Top. Microbiol Immunol. 81:130–139.Google Scholar
  56. 56.
    Stähli, C., Staehelin, T., Miggiano, V., Schmidt, J., and Haring, P., 1980, High frequencies of antigen specific hybridomas: Dependence on immunization parameters and prediction by spleen cell analysis, J. Immunol. Meth. 32:297–304.CrossRefGoogle Scholar
  57. 57.
    Eshhar, Z., Ofarim, M., and Waks, T., 1980, Generation of hybridomas secreting murine re-aginic antibodies of anti-DNP specificity, J. Immunol. 124:775–780.PubMedGoogle Scholar
  58. 58.
    Trucco, M. M., Stocker J. W., and Ceppellini, R., 1978, Monoclonal antibodies against human lymphocyte antigens, Nature 273:666–668.PubMedCrossRefGoogle Scholar
  59. 59.
    Hengartner, H., Luzzati, A., and Schreier, M., 1978, Fusion of in vitro immunized lymphoid cells with × 63Ag8, Curr. Top. Microbiol. Immunol. 81:92–99.PubMedGoogle Scholar
  60. 60.
    Reading, C. L., 1982, In vitro immunization for the production of monoclonal antibodies, J. Immunol. Meth. 53:261–291.CrossRefGoogle Scholar
  61. 61.
    Luben, R., Bohlen, P., and Guillemin, R., 1982, Monoclonal antibodies to hypothalamic growth hormone releasing factor with picomoles of antigens, Science 218:887–889.PubMedCrossRefGoogle Scholar
  62. 62.
    Pardue, R. L., Brady, R. C., Perry, G. W., and Dedman, J. R., 1983, Production of monoclonal antibodies against calmodulin by in vitro immunization of spleen cells, J. Cell Biol. 96:1149–1154.PubMedCrossRefGoogle Scholar
  63. 63.
    Kozbor, D., and Roder, J., 1984, In vitro stimulated lymphocytes as a source of human hybridomas, Eur. J. Immunol. 14:23–27.PubMedCrossRefGoogle Scholar
  64. 64.
    Köhler, G., and Milstein, G., 1976, Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion, Eur. J. Immunol. 6:511–519.PubMedCrossRefGoogle Scholar
  65. 65.
    Kearney F., Radbruch A., Liesegang B., and Rajewsky, K., 1979, A new mouse myeloma cell line which has lost immunoglobulin expression but permits the construction of antibody secreting hybrid cell lines, J. Immunol. 123:1548–1550.PubMedGoogle Scholar
  66. 66.
    Shulman, M., Wilde, C. D., and Köhler, G., 1978, A better cell line for making hybridomas secreting specific antibodies, Nature 276:269–270.PubMedCrossRefGoogle Scholar
  67. 67.
    Trowbridge, I. S., 1978, Interspecies spleen myeloma hybrid producing monoclonal antibodies against mouse lymphocyte surface glycoprotein T200, J. Exp. Med. 148:313–323.PubMedCrossRefGoogle Scholar
  68. 68.
    Margulies, D. H., Kuehl, W. M., and Scharff, M. D., 1976, Somatic cell hybridization of mouse myeloma cells, Cell 8:405–415.PubMedCrossRefGoogle Scholar
  69. 69.
    Taggart, R. T., and Samloff, I. M., 1983, Stable antibody producing murine hybridomas, Science 219:1228–1230.PubMedCrossRefGoogle Scholar
  70. 70.
    Galfrè, G., Milstein, C., and Wright, B., 1979, Rat x rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG, Nature 277:131–133.PubMedCrossRefGoogle Scholar
  71. 71.
    Kilmartin, J. V., Wright, B., and Milstein, C., 1982, Rat monoclonal antitubulin antibodies derived by using a new nonsecreting rat cell line, J. Cell Biol. 93:576–582.CrossRefGoogle Scholar
  72. 72.
    Bazin, H., 1982, Production of rat monoclonal antibodies with the LOU rat nonsecreting IR983F myeloma cell line, in Protides of the Biological Fluids (H. Peeters, ed.), Pergamon Press, Oxford, pp. 615–618.Google Scholar
  73. 73.
    Adams, R. L. P., 1980, Cell Cujture for Biochemists, Elsevier/North-Holland, Amsterdam.Google Scholar
  74. 74.
    Cleveland, W. L., Erlanger, B. F., 1983, Routine large-scale production of monoclonal antibodies in a protein free culture medium, J. Immunol. Meth. 56:221–234.CrossRefGoogle Scholar
  75. 75.
    Kovar, J., and Franek, F., 1984, Serum-free medium for hybridoma and parental myeloma cell cultivation—A novel composition of growth-supporting substances, ImmunoJ. Lett. 7:339–345.CrossRefGoogle Scholar
  76. 76.
    Norwood, T. H., Zeigler, C. J., and Martin, G. M., 1976, Dimethyl sulfoxide enhances polyethylene glycol mediated cell fusion, Somat. Cell Genet. 2:263–270.PubMedCrossRefGoogle Scholar
  77. 77.
    Gefter, M. L., Margulies, D. H., and Scharff, M. D., 1977, A simple method for polyethylene glycol promoted hybridization of mouse myeloma cells, Somat. Cell Genet. 3:231–236.PubMedCrossRefGoogle Scholar
  78. 78.
    Lernhardt, W., Anderson, J., Coutinho, A., and Melchers, F., 1978, Cloning of murine transformed cell lines in suspension culture with efficiencies near 100%, Exp. Cell Res. 111:309–316.PubMedCrossRefGoogle Scholar
  79. 79.
    Sharon, J., Morrison, S. L., and Kabat, E. A., 1979, Detection of specific hybridoma clones by replica immunoadsorption of their secreted antibodies, Proc. Natl. Acad. Sci. USA 76:1420–1424.PubMedCrossRefGoogle Scholar
  80. 80.
    Parks, D. R., Bryan, V. M., Oi, V. T., and Herzenberg, L. A., 1979, Antigen specific identification and cloning of hybridomas with a fluorescence-activated cell sorter, Proc. Natl. Acad. Sci. USA 76:1962–1966.PubMedCrossRefGoogle Scholar
  81. 81.
    Lefkovitz, I., 1979, Limiting dilution analysis, in: Immunological Methods, Volume 1 (I. Lef-kovits and B. Pernis, eds.), Academic Press, New York, pp. 355–370.Google Scholar
  82. 82.
    Goding, J. W., 1978, Staphylococcal protein A as an immunological reagent, J. ImmunoJ. Meth. 20:241–253.CrossRefGoogle Scholar
  83. 83.
    Marshak-Rothstein, A., Fink, P., Gridley, T., Taulet, D. H., Bevan, M. J., Gefter, M. L., Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus, J. Immunol. 122:2491–2497.Google Scholar
  84. 84.
    Secher, D. S., and Burke, D. C., 1980, A monoclonal antibody for large scale purification of human leucocyte interferon, Nature 285:446–450.PubMedCrossRefGoogle Scholar
  85. 85.
    Moshley-Rosen, D., and Fuchs, S., 1981, Monoclonal anti-acetylcholine receptor antibodies directed against the cholinergic binding site, Biochemistry 20:5920–5924.CrossRefGoogle Scholar
  86. 86.
    Burstin, S. J., Spriggs, D. R., and Fields, B. N., 1982, Evidence for functional domains on the Reovirus type 3 hemagglutinin, Virology 117:146–155.PubMedCrossRefGoogle Scholar
  87. 87.
    Eshhar, Z., Kim, J. B., Bernard, G., Collins, W. P., Gilad, S., Lindner, H. R., and Kohen, F., 1981, Use of monoclonal antibodies to pregnandiol-3-glucoronide for the development of a solid-phase chemiluminescence immunoassay, Steroids 38:89–106.PubMedCrossRefGoogle Scholar
  88. 88.
    Kim, J. B., Bernard, G. J., Collins, W. P., Kohen, F., Lindner, H. R., and Eshhar, Z., 1982, Measurement of plasma estradiol-17 by solid-phase chemiluminescence immunoassay, Clin. Chem. 28:1120–1124.PubMedGoogle Scholar
  89. 89.
    Kohen, F., Lichter, S., Eshhar, Z., and Lindner, H. R., 1982, Preparation of monoclonal antibodies able to discriminate between testosterone and 5α-dihydrotestosterone, Steroids 39:453–459.PubMedCrossRefGoogle Scholar
  90. 90.
    Yalow, R., 1978, Radioimmunoassay: A probe for the fine structure of biologic systems, Science 200:1236–1245.PubMedCrossRefGoogle Scholar
  91. 91.
    Eshhar, Z., Ben-Izhak, R., Ariel, N., and Arnon, R., 1983, Differences among individual CEA preparations and carcinomas of different origin as detected by monoclonal anti-CEA antibodies, in: Protides of the Biological Fluids, Volume 31 (H. Peeters, ed.), Pergamon Press, pp. 929–932.Google Scholar
  92. 92.
    Moller, B. (ed.), 1983, Functional T cell subsets defined by monoclonal antibodies, Immunol. Rev. 74:1–160.Google Scholar
  93. 93.
    Ledbetter, J. A., and Herzenberg, L. A., 1979, Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens, Immunol. Rev. 47:63–90.PubMedCrossRefGoogle Scholar
  94. 94.
    Reinherz, E. L., Kung, P. C., Golstein, G., and Schlossman, S. F., 1979, Separation of functional subsets of human T cells by monoclonal antibody, Proc. Natl. Acad. Sci. USA 76:4061–4065.PubMedCrossRefGoogle Scholar
  95. 95.
    Guesdon, J.-R., Ternynck, T., and Avrameas, S., 1979, The use of avidin-biotin interaction in immunoenzymatic techniques, J. Histochem. Cytochem. 27:1131–1139.PubMedCrossRefGoogle Scholar
  96. 96.
    Hsu, S.-M., Raine, L., and Fänger, H., 1981, The use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques, J. Histochem. Cytochem. 29:577–596.PubMedCrossRefGoogle Scholar
  97. 97.
    Yachi, A., Imai, K., Fujita, H., Horiya, Y., Tanda, M., Endo, T., Tsujisakai, M., and Kawaharada, M., 1984, Immunohistochemical distribution of the antigenic determinants detected by monoclonal antibodies to carcinoembryonic antigen, J. Immunol. 132:2998–3004.PubMedGoogle Scholar
  98. 98.
    Meuer, S. C., Fitzgerald, K. A., Hussey, R. E., Hodgdon, J. C., Schlossman, S. F., and Reinherz, E. L., 1983, Clonotypic structures involved in antigen-specific human T cell function, J. Exp. Med. 157:705–719.PubMedCrossRefGoogle Scholar
  99. 99.
    Haskins, K., Kubo, R., White, J., Pigeon, M., Kappler, J., and Marrack, P., 1983, The major histocompatibility complex—Restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody, J. Exp. Med. 157:1149–1169.PubMedCrossRefGoogle Scholar
  100. 100.
    Staerz, U., Pasternack, M. S., Klein, J. R., Benedetto, J. D., and Bevan, M. J., 1984, Monoclonal antibodies specific for a murine cytotoxic T lymphocyte clone, Proc. Natl. Acad. Sci. USA 81:1799–1804.CrossRefGoogle Scholar
  101. 101.
    Frackelton, A. R., and Rotman, B., 1980, Functional diversity of antibodies elicited by bacterial β-D-galactosidase, J. Biol. Chem. 255:5286–5290.PubMedGoogle Scholar
  102. 102.
    Eshhar, Z., Blatt, C., Bergman, Y., and Haimovich, J., 1979, Induction of secretion of IgM from cells of the B cell line 38C-13 by somatic cell hybridization, J. Immunol. 122:2430–2434.PubMedGoogle Scholar
  103. 103.
    Springer, T. A., 1983, Quantitation of hybridoma immunoglobulin and selection of myeloma or specific light chain loss variants, Meth. Enzymol. 92:147–160.PubMedCrossRefGoogle Scholar
  104. 104.
    Allison, J. P., McIntyre, B. W., and Bloch, D., 1982, Tumor specific antigen of murine T lymphoma defined with monoclonal antibody, J. Immunol. 129:2293–2296.PubMedGoogle Scholar
  105. 105.
    Haaijman, J. J., Deen, C., Krose, C. J. M., Zijlstra, J. J., Coden, J., and Radl, J., 1984, A jungle full of pitfalls, Immunol. Today 5:56–58.Google Scholar
  106. 106.
    Catt, K. J., and Tregear, G., 1967, Solid phase radioimmunoassay in antibody coated tubes, Science 158:1570–1572.PubMedCrossRefGoogle Scholar
  107. 107.
    Pierce, S. K., and Klinman, N. R., 1976, Allogeneic carrier specific enhancement of hapten-specific secondary B cell responses, J. Exp. Med. 144:1254–1262.PubMedCrossRefGoogle Scholar
  108. 108.
    Tsu, T. T., and Herzenberg, L. A., 1980, Solid phase radioimmunoassays, in: Selected Methods in Cellular Immunology (B. B. Mishel and S. M. Shiigi, eds.) Freeman, San Francisco, pp. 373–397.Google Scholar
  109. 109.
    Nowinski, R. C., Lostrum, M. E., Tarn, M. R., Stone, M. R., and Burnette, W. N., 1979, The isolation of hybrid cell lines producing monoclonal antibodies against the p15(E) protein of ectotropic murine leukemia virus, Virology 93:111–126.PubMedCrossRefGoogle Scholar
  110. 110.
    Cy, P. L., Prowse, S. J., and Jenkin, C. R., 1970, Isolation of pure IgG1, IgG2a, and IgG2b immunoglobulins from mouse serum using protein A-Sepharose, Immunochemistry 15:429–436.Google Scholar
  111. 111.
    Mason, D. W., and Williams, A. F., 1980, The kinetics of antibody binding to membrane antigens in solution and at the cell surface, Biochem. J. 187:1–20.PubMedGoogle Scholar
  112. 112.
    Kincade, P. W., Lee, G., Sun, L., and Watanabe, T., 1981, Monoclonal rat antibodies to murine IgM determinants, J. Immunol. Meth. 42:17–26.CrossRefGoogle Scholar
  113. 113.
    Taylor, R. B., Duffus, W. P. H., Raff, M., and de Pétris, S., 1971, Redistribution and pinocytosis of lymphocyte surface immunoglobulin molecules by anti-immunoglobulin antibodies, Nature 233:225–229.CrossRefGoogle Scholar
  114. 114.
    Engvall, E., and Pesce, A. J. (eds.), 1978, Quantitative enzyme immunoassay, Scand. J. Immunol. 8(Suppl. 7) Blackwell Scientific Publishers, Oxford.Google Scholar
  115. 115.
    Engvall, E., 1980, Enzyme immunoassay ELISA and EMIT, Meth. Enzymol. 70:419–438.PubMedCrossRefGoogle Scholar
  116. 116.
    Maggio, E. T., 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Florida.Google Scholar
  117. 117.
    Calvener, J. C., Harris, A. W., Mandel, T. E., Whitelaw, A., and Ferber, E., 1981, Alkaline phosphatase in hematopoietic tumor cell lines of the mouse: High activity in cells of the B lymphoid lineage, J. Immunol. 126:1974–1977.Google Scholar
  118. 118.
    Williams, W. J., Beutler, E., Ersler, A. J., and Rundles, R. W., 1977, Hematology, 2nd ed., McGraw-Hill, New York.Google Scholar
  119. 119.
    O’Sullivan, M. J., Gremmi, E., Simmonds, A. D., Chiefegotti, G., Heyderman, E., Bridges, J. W., and Marks, V., 1979, A comparison of the ability of β-galactosidases and horseradish peroxidase enzyme-antibody conjugates to detect specific antibodies, J. Immunol. Meth. 31:247–250.CrossRefGoogle Scholar
  120. 120.
    Chandler, H. M., Cox, J. C., Healey, K., MacGregor, A., Premier, R. R., and Hurrell, J. G. R., 1982, An investigation of the use of urease-antibody conjugates in enzyme immunoassays, J. Immunol. Meth. 53:187–198.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Zelig Eshhar
    • 1
  1. 1.Department of Chemical ImmunologyWeizmann Institute of ScienceRehovotIsrael

Personalised recommendations