Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1970 Aug 1;132(2):261–282. doi: 10.1084/jem.132.2.261

CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES

I. ENHANCEMENT OF PRIMARY AND SECONDARY ANTI-HAPTEN ANTIBODY RESPONSES BY CARRIER PREIMMUNIZATION

David H Katz 1, William E Paul 1, Edmond A Goidl 1, Baruj Benacerraf 1
PMCID: PMC2138738  PMID: 4101344

Abstract

Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ε-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. ASHLEY H., OVARY Z. EFFECT OF BOVINE GAMMA GLOBULIN ON SUBSEQUENT IMMUNIAZTION WITH DINITROPHENYLATED BOVINE GAMMA GLOBULIN. Proc Soc Exp Biol Med. 1965 Jun;119:311–314. doi: 10.3181/00379727-119-30165. [DOI] [PubMed] [Google Scholar]
  2. BENACERRAF B., GELL P. G. Studies on hypersensitivity. III. The relation between delayed reactivity to the picryl group of conjugates and contact sensitivity. Immunology. 1959 Jul;2:219–229. [PMC free article] [PubMed] [Google Scholar]
  3. BENACERRAF B., LEVINE B. B. Immunological specificity of delayed and immediate hypersensitivity reactions. J Exp Med. 1962 May 1;115:1023–1036. doi: 10.1084/jem.115.5.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BENACERRAF B., OJEDA A., MAURER P. H. STUDIES ON ARTIFICIAL ANTIGENS. II. THE ANTIGENICITY IN GUINEA PIGS OF ARSANILIC ACID CONJUGATES OF COPOLYMERS OF D- OR L-ALPHA-AMINO ACIDS. J Exp Med. 1963 Dec 1;118:945–952. doi: 10.1084/jem.118.6.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BENACERRAF B., OVARY Z., BLOCH K. J., FRANKLIN E. C. Properties of guinea pig 7S antibodies. I. Electrophoretic separation of two types of guinea pig 7S antibodies. J Exp Med. 1963 Jun 1;117:937–949. doi: 10.1084/jem.117.6.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BOREK F., SILVERSTEIN A. M. SPECIFICITY OF GUINEA-PIG ANTIBODIES AND DELAYED HYPERSENSITIVITY. Nature. 1965 Jan 16;205:299–300. doi: 10.1038/205299a0. [DOI] [PubMed] [Google Scholar]
  7. BOYDEN S. V. The adsorption of proteins on erythrocytes treated with tannic acid and subsequent hemagglutination by antiprotein sera. J Exp Med. 1951 Feb;93(2):107–120. doi: 10.1084/jem.93.2.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CINADER B., PEARCE J. H. The specificity of acquired immunological tolerance to azo proteins. Br J Exp Pathol. 1958 Feb;39(1):8–29. [PMC free article] [PubMed] [Google Scholar]
  9. COE J. E., SALVIN S. B. THE IMMUNE RESPONSE IN THE PRESENCE OF DELAYED HYPERSENSITIVITY OF CIRCULATING ANTIBODY. J Immunol. 1964 Sep;93:495–510. [PubMed] [Google Scholar]
  10. Claman H. N., Chaperon E. A., Triplett R. F. Thymus-marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1167–1171. doi: 10.3181/00379727-122-31353. [DOI] [PubMed] [Google Scholar]
  11. DUTTON R. W., BULMAN H. N. THE SIGNIFICANCE OF THE PROTEIN CARRIER IN THE STIMULATION OF DNA SYNTHESIS BY HAPTEN-PROTEIN CONJUGATES IN THE SECONDARY RESPONSE. Immunology. 1964 Jan;7:54–64. [PMC free article] [PubMed] [Google Scholar]
  12. EISEN H. N., CARSTEN M. E., BELMAN S. Studies of hypersensitivity to low molecular weight substances. III. The 2,4-dinitrophenyl group as a determinant in the preciptin reaction. J Immunol. 1954 Nov;73(5):296–308. [PubMed] [Google Scholar]
  13. FARAH F. S., KERN M., EISEN H. N. The preparation and some properties of purified antibody specific for the 2,4-dinitrophenyl group. J Exp Med. 1960 Dec 1;112:1195–1210. doi: 10.1084/jem.112.6.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GELL P. G., BENACERRAF B. Studies on hypersensitivity. IV. The relationship between contact and delayed sensitivity: a study of the specificity of cellular immune reactions. J Exp Med. 1961 Mar 1;113:571–585. doi: 10.1084/jem.113.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Green I., Benacerraf B., Stone S. H. The effect of the amount of mycobacterial adjuvants on the immune response of strain 2, strain 13 and Hartley strain guinea pigs to DNP-PLL and DNP-GL. J Immunol. 1969 Sep;103(3):403–412. [PubMed] [Google Scholar]
  17. Green I., Paul W. E., Benacerraf B. Hapten carrier relationships in the DNP-PLL foreign albumin complex system: induction of tolerance and stimulation of cells in vitro. J Exp Med. 1968 Jan 1;127(1):43–53. doi: 10.1084/jem.127.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Green I., Paul W. E., Benacerraf B. The behavior of hapten-poly-L-lysine conjugates as complete antigens in genetic responder and as haptens in nonresponder guinea pigs. J Exp Med. 1966 May 1;123(5):859–879. doi: 10.1084/jem.123.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LEVINE B. B., OJEDA A., BENACERRAF B. BASIS FOR THE ANTIGENICITY OF HAPTEN-POLY-L-LYSINE CONJUGATES IN RANDOM-BRED GUINEA PIGS. Nature. 1963 Nov 9;200:544–546. doi: 10.1038/200544a0. [DOI] [PubMed] [Google Scholar]
  20. LEVINE B. B. STUDIES ON DELAYED HYPERSENSITIVITY. I. INFERENCES ON THE COMPARATIVE BINDING AFFINITIES OF ANTIBODIES MEDIATING DELAYED AND IMMEDIATE HYPERSENSITIVITY REACTIONS IN THE GUINEA PIG. J Exp Med. 1965 Jun 1;121:873–888. doi: 10.1084/jem.121.6.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. LEVINE B. B. Studies on the dimensions of the rabbit antibenzylpenicilloyl antibody-combing sites. J Exp Med. 1963 Jan 1;117:161–183. doi: 10.1084/jem.117.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levine B. B. Specificity of the anamnestic response to a double hapten conjugate in guinea pigs primed with a single hapten. J Immunol. 1967 Dec;99(6):1173–1177. [PubMed] [Google Scholar]
  23. Little J. R., Counts R. B. Affinity and heterogeneity of antibodies induced by epsilon-2,4-dinitrophenylinsulin. Biochemistry. 1969 Jul;8(7):2729–2736. doi: 10.1021/bi00835a006. [DOI] [PubMed] [Google Scholar]
  24. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  25. Miller J. F., Mitchell G. F. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):801–820. doi: 10.1084/jem.128.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mitchell G. F., Miller J. F. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J Exp Med. 1968 Oct 1;128(4):821–837. doi: 10.1084/jem.128.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. NUSSENZWEIG V., BENACERRAF B. STUDIES ON THE PROPERTIES OF FRAGMENTS OF GUINEA PIG GAMMA-1 AND GAMMA-2 ANTIBODIES OBTAINED BY PAPAIN DIGESTION AND MILD REDUCTION. J Immunol. 1964 Dec;93:1008–1014. [PubMed] [Google Scholar]
  28. Nussenzweig V., Green I., Vassalli P., Benacerraf B. Changes in the proportion of guinea-pig gamma-1 and gamma-2 antibodies during immunization and the cellular localization of these immunoglobulins. Immunology. 1968 May;14(5):601–609. [PMC free article] [PubMed] [Google Scholar]
  29. OETTGEN H. F., BINAGHI R. A., BENACERRAF B. HEXOSE CONTENT OF GUINEA PIG GAMMA-1 AND GAMMA-2 IMMUNOGLOBULINS. Proc Soc Exp Biol Med. 1965 Feb;118:336–342. [PubMed] [Google Scholar]
  30. OVARY Z., BENACERRAF B. IMMUNOLOGICAL SPECIFICITY OF THE SECONDARY RESPONSE WITH DINITROPHENYLATED PROTEINS. Proc Soc Exp Biol Med. 1963 Oct;114:72–76. doi: 10.3181/00379727-114-28589. [DOI] [PubMed] [Google Scholar]
  31. Parker C. W., Gott S. M., Johnson M. C. The antibody response to a 2,4-dinitrophenyl peptide. Biochemistry. 1966 Jul;5(7):2314–2326. doi: 10.1021/bi00871a021. [DOI] [PubMed] [Google Scholar]
  32. Paul W. E., Siskind G. W., Benacerraf B., Ovary Z. Secondary antibody responses in haptenic systems: cell population selection by antigen. J Immunol. 1967 Oct;99(4):760–770. [PubMed] [Google Scholar]
  33. Paul W. E., Siskind G. W., Benacerraf B. Specificity of cellular immune responses. Antigen concentration dependence of stimulation of DNA synthesis in vitro by specifically sensitized cells, as an expression of the binding characteristics of cellular antibody. J Exp Med. 1968 Jan 1;127(1):25–42. doi: 10.1084/jem.127.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Paul W. E., Siskind G. W., Benacerraf B. Studies on the effect of the carrier molecule on antihapten antibody synthesis. II. Carrier specificity of anti-2,4-dinitrophenyl-poly-l-lysine antibodies. J Exp Med. 1966 Apr 1;123(4):689–705. doi: 10.1084/jem.123.4.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Paul W. E., Thorbecke G. J., Siskind G. W., Benacerraf B. The effect of dose in tolerance induction on the subsequent response to a cross-reactive antigen. Immunology. 1969 Jul;17(1):85–92. [PMC free article] [PubMed] [Google Scholar]
  36. Rajewsky K., Rottländer E., Peltre G., Müller B. The immune response to a hybrid protein molecule; specificity of secondary stimulation and of tolerance induction. J Exp Med. 1967 Oct 1;126(4):581–606. doi: 10.1084/jem.126.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rajewsky K., Schirrmacher V., Nase S., Jerne N. K. The requirement of more than one antigenic determinant for immunogenicity. J Exp Med. 1969 Jun 1;129(6):1131–1143. doi: 10.1084/jem.129.6.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rittenberg M. B., Campbell D. H. Heterologous carriers in the anamnestic antihapten response. J Exp Med. 1968 Apr 1;127(4):717–730. doi: 10.1084/jem.127.4.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. SALVIN S. B., SMITH R. F. Specificity of allergic reactions. II. Azoproteins in the anamnestic response. Proc Soc Exp Biol Med. 1960 Aug-Sep;104:584–590. doi: 10.3181/00379727-104-25916. [DOI] [PubMed] [Google Scholar]
  40. SALVIN S. B., SMITH R. F. The specificity of allergic reactions. I. Delayed versus Arthus hypersensitivity. J Exp Med. 1960 Apr 1;111:465–483. doi: 10.1084/jem.111.4.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  42. SILVERSTEIN A. M., GELL P. G. Delayed hypersensitivity to hapten-protein conjugates. II. Anti-hapten specificity and the heterogeneity of the delayed response. J Exp Med. 1962 May 1;115:1053–1064. doi: 10.1084/jem.115.5.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. STAVITSKY A. B. Micromethods for the study of proteins and antibodies. I. Procedure and general applications of hemagglutination and hemagglutination-inhibition reactions with tannic acid and protein-treated red blood cells. J Immunol. 1954 May;72(5):360–367. [PubMed] [Google Scholar]
  44. Schierman L. W., McBride R. A. Adjuvant activity of erythrocyte isoantigens. Science. 1967 May 5;156(3775):658–659. doi: 10.1126/science.156.3775.658. [DOI] [PubMed] [Google Scholar]
  45. Small P. A., Jr, Lamm M. E. Polypeptide chain structure of rabbit immunoglobulins. I. gamma-G-immunoglobulin. Biochemistry. 1966 Jan;5(1):259–267. doi: 10.1021/bi00865a034. [DOI] [PubMed] [Google Scholar]
  46. Steiner L. A., Eisen H. N. The relative affinity of antibodies synthesized in the secondary response. J Exp Med. 1967 Dec 1;126(6):1185–1205. doi: 10.1084/jem.126.6.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stupp Y., Yoshida T., Paul W. E. Determination of antibody-hapten equilibrium constants by an ammonium sulfate precipitation technique. J Immunol. 1969 Sep;103(3):625–627. [PubMed] [Google Scholar]
  48. WHITE R. G., JENKINS G. C., WILKINSON P. C. The production of skin-sensitizing antibody in the guinea-pig. Int Arch Allergy Appl Immunol. 1963;22:156–165. doi: 10.1159/000229362. [DOI] [PubMed] [Google Scholar]

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

RESOURCES