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. 1973 Oct 31;138(5):1213–1229. doi: 10.1084/jem.138.5.1213

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

Ethan M Shevach 1, Alan S Rosenthal 1
PMCID: PMC2139446  PMID: 4126770

Abstract

A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F1 and the resultant stimulation was measured. No stimulation was seen when column-purified F1 lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F1 T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F1 were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F1 cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F1 T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.

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Selected References

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

  1. Davie J. M., Paul W. E., Green I. Genetic control of the immune response of inbred guinea pigs to 2,4-dinitrophenyl guinea pig albumin. Frequency of antigen-binding lymphocytes and avidity of antibodies secreted by plaque-forming cells. J Immunol. 1972 Aug;109(2):193–200. [PubMed] [Google Scholar]
  2. Dunham E. K., Unanue E. R., Benacerraf B. Antigen binding and capping by lymphocytes of genetic nonresponder mice. J Exp Med. 1972 Aug 1;136(2):403–408. doi: 10.1084/jem.136.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ellman L., Green I., Benacerraf B. Identification of the cell population responding to DNP-GL in lethally irradiated strain 13 chimeric guinea pigs reconstituted with strain 13 bone marrow and (2 x 13) F 1 lymph node and spleen cells. Cell Immunol. 1970 Oct;1(4):445–454. doi: 10.1016/0008-8749(70)90020-1. [DOI] [PubMed] [Google Scholar]
  4. Foerster J., Green I., Lamelin J. P., Benacerraf B. Transfer of responsiveness to hapten conjugates of poly-L-lysine and of a copolymer of L-glutamic acid and L-lysine to lethally irradiated nonresponder guinea pigs by bone marrow or lymph node and spleen cells from responder guinea pigs. J Exp Med. 1969 Nov 1;130(5):1107–1122. doi: 10.1084/jem.130.5.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Green I., Paul W. E., Benacerraf B. A study of the passive transfer of delayed hypersensitivity to DNP-poly-L-lysine and DNP-GL in responder and nonresponder guinea pigs. J Exp Med. 1967 Nov 1;126(5):959–967. doi: 10.1084/jem.126.5.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Hämmerling G. J., Masuda T., McDevitt H. O. Genetic control of the immune response. Frequency and characteristics of antigen-binding cells in high and low responder mice. J Exp Med. 1973 May 1;137(5):1180–1200. doi: 10.1084/jem.137.5.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KANTOR F. S., OJEDA A., BENCARERRAF B. Studies on artifical antigens. I. Antigenicity of DNP-polylysine and DNP copolymer of lysine and glutamic acid in guinea pigs. J Exp Med. 1963 Jan 1;117:55–69. doi: 10.1084/jem.117.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Rosenthal A. S., Davie J. M., Rosenstreich D. L., Blake J. T. Depletion of antibody-forming cells and their precursors from complex lymphoid cell populations. J Immunol. 1972 Jan;108(1):279–281. [PubMed] [Google Scholar]
  11. 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]
  12. 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]

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