Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Apr 1;157(4):1287–1299. doi: 10.1084/jem.157.4.1287

Antigen-presenting cells from nonresponder strain 2 guinea pigs are fully competent to present bovine insulin B chain to responder strain 13 T cells. Evidence against a determinant selection model and in favor of a clonal deletion model of immune response gene function

PMCID: PMC2186989  PMID: 6187889

Abstract

To test directly the determinant selection hypothesis of immune response gene function, we primed strain 13 T lymphocytes in vitro with allogeneic bovine insulin pulsed strain 2 macrophages. Strain 2 macrophages were found to be fully competent to present bovine insulin B chain to strain 13 T cells despite the fact that strain 2 guinea pigs are normally totally unresponsive to this antigen. These results are incompatible with a strict interpretation of the determinant selection hypothesis, which would have predicted that strain 2 macrophages would have been restricted to the presentation of A chain loop determinants. In addition, a comparison of the reactivity profiles of self-Ia- and allo-Ia-restricted strain 13 T cells to a series of synthetic B chain peptide fragments revealed that the allo-Ia-restricted populations could be activated by autologous guinea pig insulin. Taken together, these observations strongly suggest that the clonal deletion of self- reactive cells is likely to be I region restricted and that nonresponsiveness to any protein antigen may result from a restriction in the T cell repertoire that is generated during ontogeny by a clonal deletion mechanism of tolerance to self.

Full Text

The Full Text of this article is available as a PDF (959.4 KB).

Selected References

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

  1. Barcinski M. A., Rosenthal A. S. Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells. J Exp Med. 1977 Mar 1;145(3):726–742. doi: 10.1084/jem.145.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  3. Clark R. B., Chiba J., Zweig S. E., Shevach E. M. T-cell colonies recognize antigen in association with specific epitopes on Ia molecules. Nature. 1982 Feb 4;295(5848):412–414. doi: 10.1038/295412a0. [DOI] [PubMed] [Google Scholar]
  4. Clark R. B., Shevach E. M. Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamic acid, L-lysine in association with nonresponder strain 13 Ia antigens. J Exp Med. 1982 Feb 1;155(2):635–640. doi: 10.1084/jem.155.2.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heber-Katz E., Schwartz R. H., Matis L. A., Hannum C., Fairwell T., Appella E., Hansburg D. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982 Apr 1;155(4):1086–1099. doi: 10.1084/jem.155.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hedrick S. M., Matis L. A., Hecht T. T., Samelson L. E., Longo D. L., Heber-Katz E., Schwartz R. H. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell. 1982 Aug;30(1):141–152. doi: 10.1016/0092-8674(82)90020-4. [DOI] [PubMed] [Google Scholar]
  7. Ishii N., Baxevanis C. N., Nagy Z. A., Klein J. Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J Exp Med. 1981 Sep 1;154(3):978–982. doi: 10.1084/jem.154.3.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Matzinger P. A one-receptor view of T-cell behaviour. Nature. 1981 Aug 6;292(5823):497–501. doi: 10.1038/292497a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  11. Schwartz R. H. A clonal deletion model for Ir gene control of the immune response. Scand J Immunol. 1978;7(1):3–10. doi: 10.1111/j.1365-3083.1978.tb00420.x. [DOI] [PubMed] [Google Scholar]
  12. Schwartz R. H., Yano A., Paul W. E. Interaction between antigen-presenting cells and primed T lymphocytes: an assessment of Ir gene expression in the antigen-presenting cell. Immunol Rev. 1978;40:153–180. doi: 10.1111/j.1600-065x.1978.tb00405.x. [DOI] [PubMed] [Google Scholar]
  13. Shevach E. M., Rosenstreich D. L., Green I. The distribution of histocompatibility antigens on T and B cells in the guinea pig. Transplantation. 1973 Aug;16(2):126–133. doi: 10.1097/00007890-197308000-00008. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells. J Exp Med. 1981 May 1;153(5):1286–1301. doi: 10.1084/jem.153.5.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Proc Natl Acad Sci U S A. 1977 May;74(5):2104–2108. doi: 10.1073/pnas.74.5.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Thomas J. W., Danho W., Bullesbach E., Föhles J., Rosenthal A. S. Immune response gene control of determinant selection. III. Polypeptide fragments of insulin are differentially recognized by T but not by B cells in insulin immune guinea pigs. J Immunol. 1981 Mar;126(3):1095–1100. [PubMed] [Google Scholar]

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

RESOURCES