Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Feb 1;147(2):554–570. doi: 10.1084/jem.147.2.554

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

PMCID: PMC2184503  PMID: 75242

Abstract

A method was established for isolating antigen-specific murine helper T cells by selective binding to antigen-pulsed macrophage (Mphi) monolayers. Sheep erythrocyte (SRBC)-primed T cells, which remained strongly adherent to SRBC-pulsed syngeneic Mphi after 20 h in culture, were markedly enriched for helper activity when tested in the in vitro antitrinitrophenol (TNP) response to TNP-SRBC. Successful binding and enrichment occurred only if the Mphi were pulsed with the specific antigen to which the T-cell donors had been primed. The genetic control governing helper function in this system was then examined by using primed F1 T cells isolated on Mphi monolayers from congenic strains bearing parental H-2 haplotypes. SRBC-primed BDF1 (H-2b X H-2d) T cells, which bound to SRBC-pulsed H-2d Mphi, subsequently functioned as helper cells in cultures containing H-2d B cells and Mphi, but not in those containing H-2b B cells and Mphi. They remained unable to collaborate with B cells of the H-2B haplotype even in the presence of additional H-2d Mphi, indicating that H-2 restriction occurs at least at the level of the B cell. Similary, primed BDF1 T cells isolated on H- 2b Mphi cooperated preferentially with H-2b B cells and Mphi. In both cases, the haplotype preference of the T cell was not due to alloreactive suppressor activity. These results suggest that primed F1 mice contain individual populations of helper T cells, each of which recognize antigen in association with a parental H-2 gene product(s) expressed during both Mphi-T cell and T cell-B cell interactions.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. 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]
  2. Ben-Sasson S. Z., Paul W. E., Shevach E. M., Green I. In vitro selection and extended culture of antigen-specific T lymphocytes. I. Description of selection culture procedure and initial characterization of selected cells. J Exp Med. 1975 Jul 1;142(1):90–105. doi: 10.1084/jem.142.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ben-Sasson S. Z., Paul W. E., Shevach E. M., Green I. In vitro selection and extended culture of antigen-specific T lymphocytes. II. Mechanisms of selection. J Immunol. 1975 Dec;115(6):1723–1730. [PubMed] [Google Scholar]
  4. Calderon J., Kiely J. M., Lefko J. L., Unanue E. R. The modulation of lymphocyte functions by molecules secreted by macrophages. I. Description and partial biochemical analysis. J Exp Med. 1975 Jul 1;142(1):151–164. doi: 10.1084/jem.142.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Click R. E., Benck L., Alter B. J. Enhancement of antibody synthesis in vitro by mercaptoethanol. Cell Immunol. 1972 Jan;3(1):156–160. doi: 10.1016/0008-8749(72)90237-7. [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. Hartmann K., Dutton R. W., McCarthy M. M., Mishell R. I. Cell components in the immune response. II. Cell attachment separation of immune cells. Cell Immunol. 1970 Jul;1(2):182–189. doi: 10.1016/0008-8749(70)90005-5. [DOI] [PubMed] [Google Scholar]
  8. Harwell L., Kappler J. W., Marrack P. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. III. Characterization of the nonspecific mediator(s) from different sources. J Immunol. 1976 May;116(5):1379–1384. [PubMed] [Google Scholar]
  9. Hoffmann M., Kappler J. W. Regulation of the immune response. II. Qualitative and quantitative differences between thymus- and bone marrow-derived lymphocytes in the recognition of antigen. J Exp Med. 1973 Mar 1;137(3):721–739. doi: 10.1084/jem.137.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoffmann M., Kappler J. W. The antigen specificity of thymus-derived helper cells. J Immunol. 1972 Jan;108(1):261–263. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Katz D. H., Chiorazzi N., McDonald J., Katz L. R. Cell interactions between histoincompatible T an B lymphocytes. IX. The failure of histoincompatible cells is not due to suppression and cannot be circumvented by carrier-priming T cells with allogeneic macrophages. J Immunol. 1976 Nov;117(5 PT2):1853–1859. [PubMed] [Google Scholar]
  14. Katz D. H., Hamaoka T., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med. 1973 Jun 1;137(6):1405–1418. doi: 10.1084/jem.137.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katz D. H., Hamaoka T., Dorf M. E., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. The H-2 gene complex determines successful physiologic lymphocyte interactions. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2624–2628. doi: 10.1073/pnas.70.9.2624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. I. Characteristics of the antigen-independent-binding of guinea pig thymocytes and lymphocytes to syngeneic macrophages. J Exp Med. 1973 Oct 1;138(4):900–924. doi: 10.1084/jem.138.4.900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med. 1975 Jan 1;141(1):138–154. doi: 10.1084/jem.141.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. Role of major histocompatibility complex gene products in delayed-type hypersensitivity. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2486–2490. doi: 10.1073/pnas.73.7.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Opitz H. G., Opitz U., Lemke H., Huget R., Flad H. D. Polyclonal stimulation of lymphocytes by macrophages. Eur J Immunol. 1976 Jul;6(7):457–461. doi: 10.1002/eji.1830060702. [DOI] [PubMed] [Google Scholar]
  24. Parish C. R., Hayward J. A. The lymphocyte surface. II. Separation of Fc receptor, C'3 receptor and surface immunoglobulin-bearing lymphocytes. Proc R Soc Lond B Biol Sci. 1974 Aug 27;187(1086):65–81. doi: 10.1098/rspb.1974.0061. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Paul W. E., Shevach E. M., Pickeral S., Thomas D. W., Rosenthal A. S. Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells. J Exp Med. 1977 Mar 1;145(3):618–630. doi: 10.1084/jem.145.3.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pierce C. W., Kapp J. A., Benacerraf B. Genetic restriction of macrophage-lymphocyte interactions in secondary antibody responses in vitro. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):563–570. doi: 10.1101/sqb.1977.041.01.065. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Rich S. S., Rich R. R. Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells. J Exp Med. 1975 Dec 1;142(6):1391–1402. doi: 10.1084/jem.142.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Theze J., Kapp J. A., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) III. Immunochemical properties of the GAT-specific suppressive factor. J Exp Med. 1977 Apr 1;145(4):839–856. doi: 10.1084/jem.145.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes II. T-cell activation by direct modification of macrophage histocompatibility antigens. J Exp Med. 1977 Apr 1;145(4):907–915. doi: 10.1084/jem.145.4.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes. I. Analysis with an in vitro primary response to soluble protein antigens. J Exp Med. 1976 Nov 2;144(5):1263–1273. doi: 10.1084/jem.144.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zinkernagel R. M., Doherty P. C. H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;. J Exp Med. 1975 Jun 1;141(6):1427–1436. doi: 10.1084/jem.141.6.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES