Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Oct 1;140(4):977–994. doi: 10.1084/jem.140.4.977

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

Peter Lonai 1, Hugh O McDevitt 1
PMCID: PMC2139625  PMID: 4547782

Abstract

In vitro antigen-induced tritiated thymidine uptake has been used to study the response of sensitized lymphocytes to (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L in responder and nonresponder strains of mice. The reaction is T-cell and macrophage dependent. Highly purified T cells (91% Thy 1.2 positive) are also responsive, suggesting that this in vitro lymphocyte transformation system is not B-cell dependent. Lymphocytes from high and low responder mice stimulated in vitro react as responders and nonresponders in a pattern identical to that seen with in vivo immunization. Stimulation occurs only if soluble antigen is added at physiological temperatures; antigen exposure at 4°C followed by washing and incubation at 37°C fails to induce lymphocyte transformation. Stimulation is specific for the immunizing antigen and does not exhibit the serologic cross-reactivity which is characteristic of these three antigens and their respective antisera. The reaction can be inhibited by anti-H-2 sera but not by anti-immunoglobulin sera. The anti-immunoglobulin sera did, however, inhibit lipopolysaccharide or pokeweed mitogen stimulation. These results suggest that the Ir-1A gene(s) are expressed in T cells, and that there are fundamental physiologic differences between T- and B-cell antigen recognition.

Full Text

The Full Text of this article is available as a PDF (926.0 KB).

Selected References

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

  1. Bechtol K. B., Wegmann T. G., Freed J. H., Grumet F. C., Chesebro B. W., Herzenberg L. A., McDevitt H. O. Genetic control of the immune response to (T,G)-A--L in C3H in equilibrium C57 tetraparental mice. Cell Immunol. 1974 Aug;13(2):264–277. doi: 10.1016/0008-8749(74)90244-5. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Doenhoff M. J., Davies A. J., Leuchars E., Wallis V. The thymus and circulating lymphocytes of mice. Proc R Soc Lond B Biol Sci. 1970 Oct 13;176(1042):69–85. doi: 10.1098/rspb.1970.0035. [DOI] [PubMed] [Google Scholar]
  4. Elfenbein G. J., Shevach E. M., Green I. Proliferation by bone marrow-derived lymphocytes in response to antigenic stimulation in vitro. J Immunol. 1972 Oct;109(4):870–874. [PubMed] [Google Scholar]
  5. Gery I., Krüger J., Spiesel S. Z. Stimulation of B-lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T 6 T 6 thymus grafts. J Immunol. 1972 Apr;108(4):1088–1091. [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Hämmerling G. J., McDevitt H. O. Antigen binding T and B lymphocytes. I. Differences in cellular specificity and influence of metabolic activity on interaction of antigen with T and B cells. J Immunol. 1974 May;112(5):1726–1733. [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Lieberman R., Paul W. E., Humphrey W., Jr, Stimpfling J. H. H-2-linked immune response (Ir) genes. Independent loci for Ir-IgG and Ir-IgA genes. J Exp Med. 1972 Nov 1;136(5):1231–1240. doi: 10.1084/jem.136.5.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lisowska-Bernstein B., Rinuy A., Vassalli P. Absence of detectable IgM in enzymatically or biosynthetically labeled thymus-derived lymphocytes. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2879–2883. doi: 10.1073/pnas.70.10.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lonai P., Wekerle H., Feldman M. Fractionation of specific antigen-reactive cells in an in vitro system of cell-mediated immunity. Nat New Biol. 1972 Feb 23;235(60):235–236. doi: 10.1038/newbio235235a0. [DOI] [PubMed] [Google Scholar]
  15. Marchalonis J. J., Cone R. E. Biochemical and biological characteristics of lymphocyte surface immunoglobulin. Transplant Rev. 1973;14:3–49. doi: 10.1111/j.1600-065x.1973.tb00101.x. [DOI] [PubMed] [Google Scholar]
  16. McDevitt H. O., Bechtol K. B., Freed J. H., Hämmerling G. J., Lonai P. The nature and site of action of the Ir-1 gene. Ann Immunol (Paris) 1974 Jan;125C(1-2):175–184. [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. McDevitt H. O., Sela M. Genetic control of the antibody response. I. Demonstration of determinant-specific differences in response to synthetic polypeptide antigens in two strains of inbred mice. J Exp Med. 1965 Sep 1;122(3):517–531. doi: 10.1084/jem.122.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McDevitt H. O., Sela M. Genetic control of the antibody response. II. Further analysis of the specificity of determinant-specific control, and genetic analysis of the response to (H,G)-A--L in CBA and C57 mice. J Exp Med. 1967 Nov 1;126(5):969–978. doi: 10.1084/jem.126.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McDevitt H. O., Tyan M. L. Genetic control of the antibody response in inbred mice. Transfer of response by spleen cells and linkage to the major histocompatibility (H-2) locus. J Exp Med. 1968 Jul 1;128(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  22. Mitchell G. F., Grumet F. C., McDevitt H. O. Genetic control of the immune response. The effect of thymectomy on the primary and secondary antibody response of mice to poly-L(tyr, glu)-poly-D, L-ala--poly-L-lys. J Exp Med. 1972 Jan;135(1):126–135. doi: 10.1084/jem.135.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rosenstreich D. L., Blake J. T., Rosenthal A. S. The peritoneal exudate lymphocyte. I. Differences in antigen responsiveness between peritoneal exudate and lymph node lymphocytes from immunized guinea pigs. J Exp Med. 1971 Nov 1;134(5):1170–1186. doi: 10.1084/jem.134.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. 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]
  27. 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]
  28. Tyan M. L. Genetically determined immune responses: in vitro studies. J Immunol. 1972 Jan;108(1):65–72. [PubMed] [Google Scholar]
  29. Vitetta E. S., Uhr J. W. Synthesis, transport, dynamics and fate of cell surface Ig and alloantigens in murine lymphocytes. Transplant Rev. 1973;14:50–75. doi: 10.1111/j.1600-065x.1973.tb00102.x. [DOI] [PubMed] [Google Scholar]
  30. Wekerle H., Lonai P., Feldman M. Fractionation of antigen reactive cells on a cellular immunoadsorbent: factors determining recognition of antigens by T-lymphocytes. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1620–1624. doi: 10.1073/pnas.69.6.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wigzell H. Specific fractionation of immunocompetent cells. Transplant Rev. 1970;5:76–104. doi: 10.1111/j.1600-065x.1970.tb00357.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES