Antigen Specific Helper Factors: An Overview after Ten Years

  • Marc Feldmann
  • Alain Fischer
  • Roger James
  • Eric Culbert
  • Mike Cecka
  • Ian Todd
  • Edward Zanders
  • Geoffrey Sunshine
  • David Katz
  • Sirkka Kontiainen


Immunology in the late 1960’s was a time of rapidly changing concepts. The functional dichotomy of T cells and B cells had been enunciated (reviewed Roitt et al., 1969, Greaves et al., 1972), the puzzle of Immune Response genes had been uncovered (Kantor et al., 1963) and receptor antibodies had been visualized on B cells but not T cells (Taylor et al., 1971). The carrier effect had been described and the phenomenon of linked recognition had suggested various molecular models (Mitchison et al., 1970) to account for the mechanism of T cell cooperation (or help). These models, represented in Fig.1, involved a ‘carrier antibody’ derived from the T cell recognizing carrier determinants on the antigen, whose ‘aptenic’ determinants interacted with B cell receptors. This could either occur with direct T-B contact, or indirectly with the ‘carrier antibody’ being released from the T cell. No formal test of the direct contact hypothesis was possible in 1971, and no direct test has yet been performed. However, a test to determine whether effective help could occur without T-B contact was feasible in tissue culture, by separating T cells and B cells by a cell impermeable membrane, which nevertheless permitted macromolecules to pass through.


Helper Cell Accessory Cell Peritoneal Exudate Cell Carrier Effect Keyhole Limpet Haemocyanin 
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  1. Andersson, J., and Melchers, F., 1981, T cell-dependent activation of resting B cells: requirement for both non-specific la-restricted soluble factors, Proc. Natl. Acad. Sci., 78:2497.Google Scholar
  2. Andersson, J., Schreier, M.H., and Melchers, F., 1980, T cell dependent B cell stimulation is H2 restricted and antigen-dependent only at the resting B cell level, Proc. Natl. Acad. Sci., U.S.A., 77:1612.Google Scholar
  3. Armerding, D., and Katz, D.H., 1974 Activation of T and B lymphocyte “in vitro”. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggered specific B lymphocyte, J. Exp. Med., 140:19.Google Scholar
  4. Ben-Neriah, Y., Wilmart, C., Lonai, P. and Givol, D., 1978, Preparation and characterisation of anti-framework antibodies to the heavy chain variable-region (VH) of mouse immunoglobulins, Eur. J. Immunol., 8:797.Google Scholar
  5. Cone, R.E., Feldmann, M., Marchalonis, J.J., and Nossal, G.J.V., 1974, Adherence of T cell receptor Ig to the macrophages surface, Immunology, 26:49.PubMedGoogle Scholar
  6. Cone, R.E., Murray, J., Rosenstein, R.W.Ptak, W., Iverson, G.M., and Gersham, R.K., The use of heteroantisera to T cell antigen binding proteins as probes for T cell receptors, in: “Immunoglobulin idiotypes and their suppression”, C. Janeway, E. ser-carz, H. Wigzell, L.C.F. Fox, Eds. Academic Press, in press.Google Scholar
  7. Delovitch, T.L., 1980, Ia antigens: signals for lymphocyte communication, Compendium in Immunology, 3:5.Google Scholar
  8. Eshhar, Z., Apte, R.N., Lowy, I., Ben-Neriah, Y., Givol, D. and Mozes, E., 1980, T cell hybridoma bearing heavy chain variable region determinants producing (T, G)-A—L specific helper factor, Nature, (London), 286:270.Google Scholar
  9. Feldmann, M., 1972, Cell interaction in the immune response “in vitro”. V. Specific collaboration with complexes of antigen and thymus derived cell immunoglobulin, J. Exp. Med., 136:737.Google Scholar
  10. Feldmann, M., and Basten, A., 1972a, Cell interaction in the immune response “in vitro”. III. Specific co-operation across a cell impermeable membrane, J. Exp. Med., 136:49.Google Scholar
  11. Feldmann, M. and Basten, A., 1972b, Cell interaction in the immune response “in vitro”. IV. Comparison of the effects of antigen specific and allogeneic thymus-derived cell factors, J. Exp. Med., 136:722.Google Scholar
  12. Feldmann, M. and Basten, S., 1972c, Cell interaction in the immune response “in vitro”. I. Metabolic activities of T cells in a collaborative antibody response, Eur. J. Immunol., 2:213.Google Scholar
  13. Feldmann, M., Boylston, A., and Hogg, N.M., 1975, Immunological effects of IgT synthesized by theta positive cell lines, Eur. J. Immunol., 5:429.Google Scholar
  14. Feldmann, M., Cone, R.E. and Marchalonis, J.J., 1973, Cell interaction in the immune response “in vitro”. IV. Mediation by T cell surface IgM, Cell. Immunol., 9:1.PubMedCrossRefGoogle Scholar
  15. Feldmann, M., Howard, J.G., and Desaymard, C., 1975, Role of antigen structure in the discrimination between tolerance and immunity by B cells, Transplant. Rev., 23:78.PubMedGoogle Scholar
  16. Feldmann, M. and Kontiainen, S., 1981, The role of antigen specific factors in the immune response, Lymphokines, 2:87.Google Scholar
  17. Feldmann, M. and Schrader, J.W., 1974, Mechanism of antigenic com-petion. II. Induction by specific T cell products, Cell. Immunol., 14:235.CrossRefGoogle Scholar
  18. Fischer, A., Zanders, E.D., Beverly, P.C.L., and Feldmann, M., 1981, Human long term helper lines, Lymphokines, Vol. 5, in press.Google Scholar
  19. Fischer, A., Beverley, P.C.L. and Feldmann, M., 1981, Long term human T helper lines producing specific helper factor reactive to influenza virus, Nature, 294:166.PubMedCrossRefGoogle Scholar
  20. Fresno, M., McVay-Boudreau, L., Nabel, G., and Cantor, H., 1981b, Antigen-specific T lymphocyte clones. II. Purification and biological characterization of an antigen-specific suppressive protein synthesized by cloned T cells, J. Exp. Med., 153:1260.PubMedCrossRefGoogle Scholar
  21. Fresno M., Nabel, G., McVay-Boudreau, L., Furthermayer, H. and Cantor, H., 1981a, Antigen-specific T lymphocyte clones. I. Characterization of a T lymphocyte clone expressing antigen-specific suppressive activity, J. Exp. Med., 153:1246.PubMedCrossRefGoogle Scholar
  22. Geha, R., 1979, Regulation of human B cell activation, Immunol. Rev., 45:275.PubMedCrossRefGoogle Scholar
  23. Gorzynski, R., and Feldmann, M., 1975, B cell heterogeneity-difference in the size of B lymphocytes responding to T dependent and T independent antigens, Cell. Immunol., 15:88.CrossRefGoogle Scholar
  24. Greaves, M., Janussy, G., Feldmann, M. and Doenhoff, M., 1974, Polyclonal mitogens and the nature of B lymphocyte activation mechanisms, in “The immune system: genes, receptors, signals”, E. Sercarz and C. Fox, Eds. Academic Press., N.Y., p. 271.Google Scholar
  25. Greaves, M.F., Owen, J.J.T., and Raff, M.C., 1973, T and B lymphocytes: origins properties and roles in immune response, in: “T and B Lymphocytes”, Eds. Elsevier-Excerpta Medica, North Holland, Amsterdam.Google Scholar
  26. Hammerling, U., Pickel, H.G., Mack, C. and Masters, D., 1976, Immunochemical study of an immunoglobulin-like molecule of murine thymocytes, Immunochemistry, 15:533.CrossRefGoogle Scholar
  27. Howie, S., and Feldmann, M., 1978, Immune response (Ir) gene expressed at macrophage B-lymphocyte interactions, Nature, (London), 273:664.CrossRefGoogle Scholar
  28. Howie, S., Parish, C.R., David, CS., McKenzie, I.F.C., Maurer, P.H. and Feldmann, M., 1979, Serological analysis of antigen specific helper factors specific for (T,G)-A—L and GAT, Eur. J. Immunol., 9:501.PubMedCrossRefGoogle Scholar
  29. Humphrey, J.H. and Grennon, D., 1981, Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal-zone macrophages, Eur. J. Immunol., 11:221.PubMedCrossRefGoogle Scholar
  30. Kantor, F.S., Ojeda, A., and Benacerraf, B.,1963, Studies on artificial antigens. I. Antigenicity of DNP-Polylysine and DNP copolymer of lysine and glutamic acid in guinea pigs, J. Exp. Med., 117:55.PubMedCrossRefGoogle Scholar
  31. Kapp, J.A., Pierce, C.W., de la Croiz, F., and Benacerraf, B., 1977, Immunosuppressive factor(s) extracted from lymphoid cells of non responder mice primed with L-glutamic acid60 -L-alanine 30-L-tyrosine10 (GAT). I. Activity and antigenic specificity, J. Exp. Med., 145:828.PubMedCrossRefGoogle Scholar
  32. Kilburn, D.G., Talbot, F.O., Teh, H.S. and Levy, J.G., 1979, A specific helper factor which enhances the cytotoxic response to a syngeneic tumour, Nature, 277:474.PubMedCrossRefGoogle Scholar
  33. Kindred, B. and Corley, R.B., 1977, A T cell-replacing factor specific for histocompatibility antigens in mice, Nature, (London), 268:531.CrossRefGoogle Scholar
  34. Kontiainen, S. and Feldmann, M., 1978, Suppressor cell induction “in vitro”. IV. Target of antigen specific suppressor factor and its genetic relationship, J. Exp. Med., 147:110.PubMedCrossRefGoogle Scholar
  35. Kontiainen, S. and Feldmann, M., 1979, Structural characteristics of antigen-specific suppressor factors: definition of ‘costant’ region and ‘variable’ region determinants, Thymus, 1:39.Google Scholar
  36. Krawinkel, U., Cramer, M., Imanishi-Kari, T.R.S., Rajewsky, K., and Makela, O., 1977, Isolated hapten-binding receptors of sensitised lymphocytes. I. Receptors from nylon wool-enriched mouse T lymphocytes lack serological markers of immunoglobulin constant domains but express heavy chain variable portions, Eur. J. Immunol.. 7:566.PubMedCrossRefGoogle Scholar
  37. Lamb, J.R., Zanders, E.D., Sanderson, A.R., Ward, P.J., Feldmann, M., Kontiainen, S., Lehner, J. and Woody, J.N., 1981, Antigen specific helper factor reacts with antibodies to human β2 microglobulin, J. Immunol., 127:231.PubMedGoogle Scholar
  38. Layton, J.E., 1980, Anti-carbohydrate activity of T cell-reactive chicken anti-mouse immunoglobulin antibodies, J. Immunol., 125:1993.Google Scholar
  39. Marchalonis, J.J., Warr, G.W., Santucci, L.A., Szenberg, A., von Fallenberg, R. and Burckhart, J.J., 1980, The immunoglobulin--like T cell receptor. IV. Quantitative cellular assay and partial characterization of a heavy chain cross-reactive with the Fd fragment of serum μ chain, Mol. Immunol., 17, 985.PubMedCrossRefGoogle Scholar
  40. McConnell, I., Lachmann, P.J., and Givol, D., 1975, Variable region (Fv) determinants on mouse lymphocytes, Immunol., 30:841.Google Scholar
  41. McDougal, J.S. and Gordon, D.S., 1977, Generation of T helper cells “in vitro”. I. Cellular and antigen requirements, J. Exp. Med., 145:676.PubMedCrossRefGoogle Scholar
  42. Melchers, F., Andersson, J., Lernhardt, W., and Schreier, M.H., 1980, H-2 unrestricted polyclonal maturation without replication of small B cells induced by antigen-activated T cell help factors, Eur. J. Immunol., 10:679.PubMedCrossRefGoogle Scholar
  43. Mitchison, N.A., Rajewsky, K. and Taylor, R.B., 1970, Co-operation of antigenic determinants and of cells in the induction of antibodies, in: “Stertz, J., Prague Symposium on Developmental aspects of antibody formation and structure”, Ed. Publishing House of the Czechoslovakia Academy of Sciences, Prague, 2:547.Google Scholar
  44. Mosier, D.E., Mond, J.J. and Goldings, E.A., 1977, The ontogeny of thymic independent antibody responses “in vitro” in normal mice and mice with an X-linked B cell defect, J. Immunol., 119:1874.PubMedGoogle Scholar
  45. Mozes, E. and Haimovich, J., 1979, Antigen-specific T cell helper factor cross reacts idiotypically with antibodies of the same specificity, Nature, (London), 278:56.CrossRefGoogle Scholar
  46. Mozes, E., Isaac, R. and Taussig, M.J., 1975, Antigen-specific T cell factors in the genetic control of the immune response to poly (Tyr GPhe)-poly D,LAla-poly Lys. Evidence or T and B cell defects in SJL mice, J. Exp. Med., 141:703.PubMedCrossRefGoogle Scholar
  47. Parish, C. and McKenzie, I.F., 1977, Direct visualization of T lymphocytes bearing Ia antigens controlled by the I-J subregion, J. Exp. Med., 146:332.PubMedCrossRefGoogle Scholar
  48. Parish, C.R., O’Neill, H.C., and Higgins, T.J., 1981, Glycosyltran-sferases and T cell recognition, Immunology Today, 2:98.CrossRefGoogle Scholar
  49. Rieber, E.P. and Riethmuller, G., 1974, Surface immunoglobulin on thymus cells. I. Increased immunogenicity of heterologous anti--Ig bound to thymus cells, Immunitaetsforsch. Exp. Klin. Immunol., 147:262.Google Scholar
  50. Roitt, I.M., Greaves, M.F., Torrigiani, G., Brostoff, J. and Play-fair, J.H.L., 1969, The cellular basis of immunological responses, Lancet, 2:367.PubMedCrossRefGoogle Scholar
  51. Rosenberg, Y.J. and Chiller, J.M., 1979, Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen, J. Exp. Med., 150:517.PubMedCrossRefGoogle Scholar
  52. Schimpl, A. and Wecker, E., 1972, Replacement of T cell function by a T cell product, Nature New Biol., (London), 237:15.Google Scholar
  53. Schreier, M.H., Tees, R. and Nordin, A.A., 1981, Establishment and characterisation of helper T cell clones: Their functional heterogeneity and effect on the B cell responses to particulate, soluble and T-independent antigens, Lymphokines, Vol 5, in press.Google Scholar
  54. Schiozawa, C., Singh, B., Rubinstein, S., and Diener, E., 1977, Molecular control of B cell triggering by antigen-specific T cell-derived helper factor, J. Immunol., 118:2199.Google Scholar
  55. Schiozawa, C., Longenecker, M.B. and Diener, E., 1980, “In vitro” cooperation of antigen-specific T cell derived helper factor, B cells, and adherent cells or their secretory product in a primary IgM response to chicken MHC antigens, J. Immunol., 125:68.Google Scholar
  56. Singer, A., Cowing, C., Hathock, K.S., Dickler, H.B. and Hodes, R.J., 1981, Role of the major histocompatibility complex in T cell activation of B cell subpopulation. Lyb-5 B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition, J. Exp. Med., 154:501.PubMedCrossRefGoogle Scholar
  57. Sprent, J., 1978, Role of H-2 gene products in the function of T helper cells from normal and chimeric mice “in vivo”, Immunol. Rev., 42:108.PubMedCrossRefGoogle Scholar
  58. Steinmann, R.M. and Conn, Z.A., 1973, Identification of a novel cell type in peripheral lymphoid organs of mice, J. Exp. Med., 137:1142.CrossRefGoogle Scholar
  59. Taniguchi, M. and Tada, R., 1974, Regulation of homocytotropic antibody formation in the rat. X. Ig T-like molecule for the induction of homocytotropic antibody response, J. Immunol., 113:1757.Google Scholar
  60. Taussig, M.J., 1974, T cell factor which can replace T cells “in vivo”, Nature, (London), 248:234.CrossRefGoogle Scholar
  61. Taussig, M.J., 1981, Studies on an antigen-specific suppressor factor produced by a T-hybrid line, Lymphokines, Vol 5 in press.Google Scholar
  62. Taussig, M.J., Mozes, E. and Isac, R., 1974, Antigen-specific thymus cell factors in the genetic control of the immune response to poly-(tyrosyl,glutamyl)-poly-DL-alanyl-poly-lysyl, J. Exp. Med., 140:301.PubMedCrossRefGoogle Scholar
  63. Taussig, M.J. and Munro, A.J., 1974, Specific co-operative T cell factor: removal by anti-H-2 but not by anti-Ig sera, Nature, (London), 251:63.CrossRefGoogle Scholar
  64. Taylor, R.B., Duffus, W.P.H., Raff, M.C. and de Petris, S., 1971, Re-distribution and pinocytosis of lymphocytes surface immunoglobulin molecules induced by anti-immunoglobulin antibody, Nature New Biol., 233:225.PubMedCrossRefGoogle Scholar
  65. Theze, J., Waterbaugh, C., Dorf, M.E. and Benacerraf, B., 1977, Immunosuppressive factor(s) for L-glutamic acid50-L-thyroxine (GT). II. Presence of I-J determinants on the GT suppressive factor, J. Exp. Med., 146:287.PubMedCrossRefGoogle Scholar
  66. Tittle, T.V. and Rittenberg, M.B., 1978, Expression of IgG memory response “in vitro” to thymus-dependent and thymus-independent antigens, Cell. Immunol., 35:180.PubMedCrossRefGoogle Scholar
  67. Tokuhisa, T., Taniguchi, M., Okumura, K. and Tada, T., 1978, An antigen-specific I-region gene product that augments the antibody response, J. Immunol., 120:414.PubMedGoogle Scholar
  68. Wood, D.D. and Cameron, P.M., 1978, The relationship between bacterial endotoxin and human B cell activating factor, J. Immunol., 121:53.PubMedGoogle Scholar
  69. Woody, J., Howie, S. and Feldmann, M., 1979, Induction of antibody-responses “in vivo” by antigen specific helper factor, Immuno-biology, 156:13.Google Scholar
  70. Zanders, E.D., Lamb, J.R., Kontiainen, S. and Lehner, T., 1980, Partial characterisation of murine and monkey helper factor to a streptococcal antigen, Immunol., 41:587.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Marc Feldmann
    • 1
  • Alain Fischer
    • 1
  • Roger James
    • 1
  • Eric Culbert
    • 1
  • Mike Cecka
    • 1
  • Ian Todd
    • 1
  • Edward Zanders
    • 1
  • Geoffrey Sunshine
    • 1
  • David Katz
    • 1
  • Sirkka Kontiainen
    • 2
  1. 1.Imperial Cancer Research Fund, Tumour Immunology Unit Department of ZoologyUniversity CollegeLondonUK
  2. 2.Department of Bacteriology and ImmunologyUniversity of Helsinki HaartmaninkatuHelsinki, 29Finland

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