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. 1977 Dec 1;146(6):1748–1764. doi: 10.1084/jem.146.6.1748

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

JW Kappler, P Marrack
PMCID: PMC2181905  PMID: 411877

Abstract

The ability of murine helper T cells primed to the antigen, sheep erythrocytes (SRBC) to cross-react with burro erythrocytes (BRBC) in the in vitro anti-trinitrophenol (TNP) response to TNP-RBC was shown to be under genetic control. Although non-H-2 genes were shown to influence the absolute level of helper activity assayed after SRBC priming, the extent of cross-reaction of SRBC-primed helpers with BRBC was shown to be controlled by an H-2-1inked Ir gene(s). H-2 haplotypes were identified which determined high, intermediate, or low response to the cross- reacting determinants and the gene(s) controlling the cross-reaction tentatively mapped to the K through I-E end of the H-2 complex. Helpers primed in F(1) mice of high x intermediate or high x low responder parents were tested for cross-reaction using B cells and macrophages (Mφ) of parental haplotypes. In each case the extent of cross-reaction was predicted by the H-2 haplotype of the B cells and Mφ, establishing the expression of the Ir gene(s) in B cells and/or Mφ a t least, but not ruling out its expression in T cells as well. The low cross-reaction seen when T cells from F(1) mice of high × low responder parents were tested on low responder B cells and Mφ was not increased by the presence of high responder Mφ, indicating the Ir gene(s) is expressed in the B cell a t least although it may be expressed in Mφ as well. These and our previously reported experiments are consistent with the hypothesis that helper T cells recognize antigen bound to the surface of B cells and Mφ in association with the product(s) of Ir gene(s) expressed on the B cell and Mφ.

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Selected References

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  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. Benacerraf B., Katz D. H. The histocompatibility-linked immune response genes. Adv Cancer Res. 1975;21:121–173. doi: 10.1016/s0065-230x(08)60972-0. [DOI] [PubMed] [Google Scholar]
  3. Benacerraf B., McDevitt H. O. Histocompatibility-linked immune response genes. Science. 1972 Jan 21;175(4019):273–279. doi: 10.1126/science.175.4019.273. [DOI] [PubMed] [Google Scholar]
  4. Bevan M. J. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975 Dec 1;142(6):1349–1364. doi: 10.1084/jem.142.6.1349. [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. Dorf M. E., Benacerraf B. Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671–3675. doi: 10.1073/pnas.72.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Falkoff R., Kettman J. Differential stimulation of precursor cells and carrier-specific thymus-derived cell activity in the in vivo reponse to heterologous erythrocytes in mice. J Immunol. 1972 Jan;108(1):54–58. [PubMed] [Google Scholar]
  9. Frelinger J. A., Neiderhuber J. E., David C. S., Shreffler D. C. Evidence for the expression of Ia (H-2-associated) antigens on thymus-derived lymphocytes. J Exp Med. 1974 Nov 1;140(5):1273–1284. doi: 10.1084/jem.140.5.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GREENWALT T. J., GAJEWSKI M., McKENNA J. L. A new method for preparing buffy coat-poor blood. Transfusion. 1962 Jul-Aug;2:221–229. doi: 10.1111/j.1537-2995.1962.tb00228.x. [DOI] [PubMed] [Google Scholar]
  11. Gordon R. D., Simpson E., Samelson L. E. In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice. J Exp Med. 1975 Nov 1;142(5):1108–1120. doi: 10.1084/jem.142.5.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greaves M. F., Brown G. Purification of human T and B lymphocytes. J Immunol. 1974 Jan;112(1):420–423. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. Hoffmann M., Kappler J. W. The antigen specificity of thymus-derived helper cells. J Immunol. 1972 Jan;108(1):261–263. [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]
  25. McDevitt H. O., Delovitch T. L., Press J. L., Murphy D. B. Genetic and functional analysis of the Ia antigens: their possible role in regulating the immune response. Transplant Rev. 1976;30:197–235. doi: 10.1111/j.1600-065x.1976.tb00221.x. [DOI] [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. Mosier D. E. A requirement for two cell types for antibody formation in vitro. Science. 1967 Dec 22;158(3808):1573–1575. doi: 10.1126/science.158.3808.1573. [DOI] [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]
  30. 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]
  31. 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]
  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. 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]
  34. 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]
  35. 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]
  36. Sachs D. H., Cone J. L. A mouse B-cell alloantigen determined by gene(s) linked to the major histocompatibility complex. J Exp Med. 1973 Dec 1;138(6):1289–1304. doi: 10.1084/jem.138.6.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shevach E. M., Paul W. E., Green I. Histocompatibility-linked immune response gene function in guinea pigs. Specific inhibition of antigen-induced lymphocyte proliferation by alloantisera. J Exp Med. 1972 Nov 1;136(5):1207–1221. doi: 10.1084/jem.136.5.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Taniguchi M., Tada T., Tokuhisa T. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response. J Exp Med. 1976 Jul 1;144(1):20–31. doi: 10.1084/jem.144.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. 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]
  44. 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]
  45. Vitetta E. S., Bianco C., Nussenzweig V., Uhr J. W. Cell surface immunoglobulin. IV. Distribution among thymocytes, bone mrrow cells, and their derived populations. J Exp Med. 1972 Jul 1;136(1):81–93. doi: 10.1084/jem.136.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Waldmann H., Pope H., Munro A. J. Cooperation across the histocompatibility barrier. Nature. 1975 Dec 25;258(5537):728–730. doi: 10.1038/258728a0. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. von Boehmer H., Hudson L., Sprent J. Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras. J Exp Med. 1975 Oct 1;142(4):989–997. doi: 10.1084/jem.142.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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