Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Jun 1;147(6):1596–1610. doi: 10.1084/jem.147.6.1596

The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages

PMCID: PMC2184325  PMID: 98610

Abstract

Using lymph node T cells from poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L- Lys[(TG)-A--L]-primed animals and B cells from animals primed with trinitrophenylated (TNP) protein or lipopolysaccharide, we have obtained anti-TNP-(TG)-A--L direct plaque-forming responses in vitro. Response to this antigen was shown to be controlled by the H-2 haplotype of the animal studied. The strain distribution of in vitro response was very similar to that previously reported by others for in vivo secondary IgG responses to (TG)-A--L. We investigated the cell types expressing the Ir gene(s) for (TG)-A--L in our cultures. F1, high responder x low responder mice were primed with (TG)-A--L. Their T cells were active in stimulating anti-TNP-(TG)-A--L responses of high responder but not low responder B cells and macrophages (MPHI), even though both preparations of B cells and Mphi were obtained from mice congenic at H-2 with one of the parents of the F1. For three low responder strains tested, of the H-2h2, H-2k, and H-2f haplotypes, the anti-TNP-(TG)-A--L response of low responder B cells and Mphis in the presence of high responder, F1 T cells could not be improved by the addition of high responder, antigen-bearing Mphis to the cultures. In one strain of the H-2a haplotype, it was shown that neither the B cells nor Mphis could be functional in anti-TNP-(TG)-A--L responses. Our results therefore suggested the Ir genes for anti-TNP-(TG)-A--L responses were expressed at least in B cells in all the low responder strains we studied, and, in mice of the H-2a haplotype, in Mphis too.

Full Text

The Full Text of this article is available as a PDF (1,013.8 KB).

Selected References

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

  1. Bale W. F., Helmkamp R. W., Davis T. P., Izzo M. J., Goodland R. L., Contreras M. A., Spar I. L. High specific activity labeling of protein with I-131 by the iodine monochloride method. Proc Soc Exp Biol Med. 1966 Jun;122(2):407–414. doi: 10.3181/00379727-122-31148. [DOI] [PubMed] [Google Scholar]
  2. Bechtol K. B., Freed J. H., Herzenberg L. A., McDevitt H. O. Genetic control of the antibody response to poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys in C3H--CWB tetraparental mice. J Exp Med. 1974 Dec 1;140(6):1660–1675. doi: 10.1084/jem.140.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Corradin G., Etlinger H. M., Chiller J. M. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol. 1977 Sep;119(3):1048–1053. [PubMed] [Google Scholar]
  4. Cowing C., Schwartz B. D., Dickler H. B. Macrophage Ia antigens. I. macrophage populations differ in their expression of Ia antigens. J Immunol. 1978 Feb;120(2):378–384. [PubMed] [Google Scholar]
  5. David C. S. Serologic and genetic aspects of murine Ia antigens. Transplant Rev. 1976;30:299–302. doi: 10.1111/j.1600-065x.1976.tb00224.x. [DOI] [PubMed] [Google Scholar]
  6. Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Festenstein H. Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant Rev. 1973;15:62–88. doi: 10.1111/j.1600-065x.1973.tb00111.x. [DOI] [PubMed] [Google Scholar]
  8. GOODMAN J. W. ON THE ORIGIN OF PERITONEAL FLUID CELLS. Blood. 1964 Jan;23:18–26. [PubMed] [Google Scholar]
  9. Greaves M. F., Brown G. Purification of human T and B lymphocytes. J Immunol. 1974 Jan;112(1):420–423. [PubMed] [Google Scholar]
  10. 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]
  11. Grumet F. C. Genetic control of the immune response. A selective defect in immunologic (IgG) memory in nonresponder mice. J Exp Med. 1972 Jan;135(1):110–125. doi: 10.1084/jem.135.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoffeld J. T., Marrack P., Kappler J. W. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. IV. Development of a model system demonstrating responsiveness of two T cell functions to HGG in vitro. J Immunol. 1976 Nov;117(5 PT2):1953–1959. [PubMed] [Google Scholar]
  13. Howie S., Feldman M. In vitro studies on H-2-linked unresponsiveness to synthetic polypeptides. III. Production of an antigen-specific T helper cell factor to (T,G)-A--L. Eur J Immunol. 1977 Jul;7(7):417–421. doi: 10.1002/eji.1830070703. [DOI] [PubMed] [Google Scholar]
  14. Jacobs D. M., Morrison D. C. Stimulation of a T-independent primary anti-hapten response in vitro by TNP-lipopolysaccharide (TNP-LPS). J Immunol. 1975 Jan;114(1 Pt 2):360–364. [PubMed] [Google Scholar]
  15. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  16. Kappler J. W., Marrack P. C. Helper T cells recognise antigen and macrophage surface components simultaneously. Nature. 1976 Aug 26;262(5571):797–799. doi: 10.1038/262797a0. [DOI] [PubMed] [Google Scholar]
  17. Kappler J. W., Marrack P. The role of H-2-linked genes in helper T-cell function. I. In vitro expression in B cells of immune response genes controlling helper T-cell activity. J Exp Med. 1977 Dec 1;146(6):1748–1764. doi: 10.1084/jem.146.6.1748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz D. H., Hamaoka T., Dorf M. E., Maurer P. H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. IV. Involvement of the immune response (Ir) gene in the control of lymphocyte interactions in responses controlled by the gene. J Exp Med. 1973 Sep 1;138(3):734–739. doi: 10.1084/jem.138.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kettman J., Dutton R. W. An in vitro primary immune response to 2,4,6-trinitrophenyl substituted erythrocytes: response against carrier and hapten. J Immunol. 1970 Jun;104(6):1558–1561. [PubMed] [Google Scholar]
  20. Lichtenberg L., Mozes E., Shearer G. M., Sela M. The role of thymus cells in the immune response to poly(Tyr, Glu)-polyD L Ala--polyLys as a function of the genetic constitution of the mouse strain. Eur J Immunol. 1974 Jun;4(6):430–434. doi: 10.1002/eji.1830040609. [DOI] [PubMed] [Google Scholar]
  21. Lonai P., McDevitt H. O. Genetic control of the immune response: in vitro stimulation of lymphocytes by (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L. J Exp Med. 1974 Oct 1;140(4):977–994. doi: 10.1084/jem.140.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  23. Marrack P., Kappler J. W. Antigen-specific and nonspecific mediatiors of T cell/B cell cooperation. II. Two helper T cells distinguished by their antigen sensitivities. J Immunol. 1976 May;116(5):1373–1378. [PubMed] [Google Scholar]
  24. McDevitt H. O., Deak B. D., Shreffler D. C., Klein J., Stimpfling J. H., Snell G. D. Genetic control of the immune response. Mapping of the Ir-1 locus. J Exp Med. 1972 Jun 1;135(6):1259–1278. doi: 10.1084/jem.135.6.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McDevitt H. O. Genetic control of the antibody response. 3. Qualitative and quantitative characterization of the antibody response to (T,G)-A--L in CBA and C57 mice. J Immunol. 1968 Mar;100(3):485–492. [PubMed] [Google Scholar]
  26. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mozes E., Isac R., Taussig M. J. Antigen-specific T-cell factors in the genetic control of the immune response to poly(Tyr,Glu)-polyDLAla--polyLys. Evidence for T- and B-cell defects in SJL mice. J Exp Med. 1975 Mar 1;141(3):703–707. doi: 10.1084/jem.141.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Munro A. J., Taussig M. J. Two genes in the major histocompatibility complex control immune response. Nature. 1975 Jul 10;256(5513):103–106. doi: 10.1038/256103a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Munro A. J., Taussig M. Complementation of immune response genes for (T,G)-A-L. Nature. 1977 Sep 22;269(5626):355–355. doi: 10.1038/269355a0. [DOI] [PubMed] [Google Scholar]
  30. Murphy D. B., Herzenberg L. A., Okumura K., Herzenberg L. A., McDevitt H. O. A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):699–712. doi: 10.1084/jem.144.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Paul W. E., Benacerraf B. Functional specificity of thymus- dependent lymphocytes. Science. 1977 Mar 25;195(4284):1293–1300. doi: 10.1126/science.320663. [DOI] [PubMed] [Google Scholar]
  32. Pierce C. W., Kapp J. A., Benacerraf B. Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro. J Exp Med. 1976 Aug 1;144(2):371–381. doi: 10.1084/jem.144.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  34. Rosenthal A. S., Barcinski M. A., Blake J. T. Determinant selection is a macrophage dependent immune response gene function. Nature. 1977 May 12;267(5607):156–158. doi: 10.1038/267156a0. [DOI] [PubMed] [Google Scholar]
  35. Schwartz R. H., Paul W. E. T-lymphocyte-enriched murine peritoneal exudate cells. II. Genetic control of antigen-induced T-lymphocyte proliferation. J Exp Med. 1976 Mar 1;143(3):529–540. doi: 10.1084/jem.143.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shearer G. M., Mozes E., Sela M. Contribution of different cell types to the genetic control of immune responses as a function of the chemical nature of the polymeric side chains (poly-L-prolyl and poly-DL-alanyl) of synthetic immunogens. J Exp Med. 1972 May 1;135(5):1009–1027. doi: 10.1084/jem.135.5.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shreffler D. C., David C. S., Cullen S. E., Frelinger J. A., Niederhuber J. E. Serological and functional evidence for further subdivision of the I regions of the H-2 gene complex. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):477–487. doi: 10.1101/sqb.1977.041.01.055. [DOI] [PubMed] [Google Scholar]
  39. Singer A., Dickler H. B., Hodes R. J. Cellular and genetic control of antibody responses in vitro. II. Ir gene control of primary IgM responses to trinitrophenyl conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys and poly-L-(His,Glu)-poly-D,L-Ala--poly-L-Lys. J Exp Med. 1977 Oct 1;146(4):1096–1107. doi: 10.1084/jem.146.4.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Snyderman R., Pike M. C., Fischer D. G., Koren H. S. Biologic and biochemical activities of continuous macrophage cell lines P388D1 and J774.1. J Immunol. 1977 Dec;119(6):2060–2066. [PubMed] [Google Scholar]
  41. Swierkosz J. E., Rock K., Marrack P., Kappler J. W. The role of H-2 linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products. J Exp Med. 1978 Feb 1;147(2):554–570. doi: 10.1084/jem.147.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Taussig M. J., Munro A. J., Campbell R., David C. S., Staines N. A. Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers. J Exp Med. 1975 Sep 1;142(3):694–700. doi: 10.1084/jem.142.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weigle W. O. The induction of a hyporesponsive state to hemocyanin. J Immunol. 1966 Feb;96(2):319–323. [PubMed] [Google Scholar]
  44. Yamashita U., Shevach E. M. The expression of Ia antigens on immunocompetent cells in the guinea pig. II. Ia antigens on macrophages. J Immunol. 1977 Nov;119(5):1584–1588. [PubMed] [Google Scholar]

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

RESOURCES