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. 1981 May 1;153(5):1286–1301. doi: 10.1084/jem.153.5.1286

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

A Singer, KS Hathcock, RJ Hodes
PMCID: PMC2186173  PMID: 6166716

Abstract

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants. Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.

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Selected References

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

  1. Bennink J. R., Doherty P. C. T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells. J Exp Med. 1978 Jul 1;148(1):128–135. doi: 10.1084/jem.148.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
  3. Biddison W. E., Payne S. M., Shearer G. M., Shaw S. Human cytotoxic T cell responses to trinitrophenyl hapten and influenza virus. Diversity of restriction antigens and specificity of HLA-linked genetic regulation. J Exp Med. 1980 Aug 1;152(2 Pt 2):204s–217s. [PubMed] [Google Scholar]
  4. Doherty P. C., Bennink J. R. Patterns of virus-immune T-cell responsiveness. Comparison of (H-2k X H-2b) leads to H-2b radiation chimeras and negatively selected H-2b lymphocytes. J Exp Med. 1979 Nov 1;150(5):1187–1194. doi: 10.1084/jem.150.5.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fathman C. G., Nabholz M. In vitro secondary mixed leukocyte reaction (MLR). II. Interaction MLR determinants expressed by F1 cells. Eur J Immunol. 1977 Jun;7(6):370–374. doi: 10.1002/eji.1830070609. [DOI] [PubMed] [Google Scholar]
  6. Hodes R. J., Handwerger B. S., Terry W. D. Synergy between subpopulations of mouse spleen cells in the in vitro generation of cell-mediated cytotoxicity: evidence for the involvement of a non-T cell. J Exp Med. 1974 Dec 1;140(6):1646–1659. doi: 10.1084/jem.140.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hodes R. J., Hathcock K. S., Singer A. Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants. J Exp Med. 1980 Dec 1;152(6):1779–1794. doi: 10.1084/jem.152.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
  9. Kappler J. W., Marrack P. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. J Exp Med. 1978 Dec 1;148(6):1510–1522. doi: 10.1084/jem.148.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Matzinger P., Mirkwood G. In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type. J Exp Med. 1978 Jul 1;148(1):84–92. doi: 10.1084/jem.148.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  13. Onoé K., Fernandes G., Good R. A. Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice. J Exp Med. 1980 Jan 1;151(1):115–132. doi: 10.1084/jem.151.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pierce S. K., Klinman N. R., Maurer P. H., Merryman C. F. Role of the major histocompatibility gene products in regulating the antibody response to dinitrophenylated poly(L-Glu55,L-Ala35,L-Phe9)n. J Exp Med. 1980 Aug 1;152(2):336–349. doi: 10.1084/jem.152.2.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Shearer G. M., Rehn T. G., Schmitt-Verhulst A. M. Role of the murine major histocompatibility complex in the specificity of in vitro T-cell-mediated lympholysis against chemically-modified autologous lymphocytes. Transplant Rev. 1976;29:222–246. doi: 10.1111/j.1600-065x.1976.tb00203.x. [DOI] [PubMed] [Google Scholar]
  17. Singer A., Cowing C., Hathcock K. S., Dickler H. B., Hodes R. J. Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function. J Exp Med. 1978 Jun 1;147(6):1611–1620. doi: 10.1084/jem.147.6.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sprent J. Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex. J Exp Med. 1978 Jun 1;147(6):1838–1842. doi: 10.1084/jem.147.6.1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stockinger H., Pfizenmaier K., Hardt C., Rodt H., Röllinghoff M., Wagner H. H-2 restriction as a consequence of intentional priming: T cells of fully allogeneic chimeric mice as well as of normal mice respond to foreign antigens in the context of H-2 determinants not encountered on thymic epithelial cells. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7390–7394. doi: 10.1073/pnas.77.12.7390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Zinkernagel R. M., Althage A., Callahan G., Welsh R. M., Jr On the immunocompetence of H-2 incompatible irradiation bone marrow chimeras. J Immunol. 1980 May;124(5):2356–2365. [PubMed] [Google Scholar]
  23. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Streilein J. W., Klein J. The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help. J Exp Med. 1978 Mar 1;147(3):897–911. doi: 10.1084/jem.147.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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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