Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1979 Nov 1;150(5):1187–1194. doi: 10.1084/jem.150.5.1187

Patterns of virus-immune T-cell responsiveness. Comparison of (H-2(k) x H-2(b)) {arrow} H-2(b) Radiation Chimeras and negatively selected H-2(b) lymphocytes

PC Doherty, Bennink JR
PMCID: PMC2185709  PMID: 115959

Abstract

Negatively selected H-2K(b)D(b) TDL can be induced to respond strongly to vaccinia virus presented in the context of both H-2K(k) and H-2D(b) when stimulated in irradiated H-2K(k)D(b) recipients. Addition of excess (H- 2K(k)D(b) x H-2K(b)D(b))F1 TDL, which are low responders to H-2D(b)-vaccinia virus, does not obviously suppress the reactivity pattern of the H-2K(b)D(b) T cells. However, lymphocytes from chimeras made by reconstituting H- 2K(b)D(b) mice with (H-2K(k)D(k) × H-2K(b)D(b))F(l) bone marrow cells make little, if any, cytotoxic T-cell response to vaccinia virus when sensitized in H-2K(k)D(b) recipients. We have thus documented one instance where the responder phenotype of T ceils from an F(l) {arrow} parent chimera is not equivalent to that associated with the H-2 type of the parental thymus. Lymphocytes from both the chimera and the H-2K(b)D(b) parent (after negative selection) are tolerant to the H-2K(k) and I-A(k) alloantigens encountered in the recipient, but the chimera T cells are also defective in their response to a neoantigen (vaccinia virus) presented in the context of H-2K(k) which the parental T cells invariably recognize. It is thus possible that at least part of the phenomenology associated with the F(l) {arrow} parent radiation chimeras reflects deletion of repertoire in the context of H-2 antigens present during thymocyte ontogeny on other than radiation-resistant thymic epithelium.

Full Text

The Full Text of this article is available as a PDF (535.8 KB).

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. Different rules govern help for cytotoxic T cells and B cells. Nature. 1978 Dec 21;276(5690):829–831. doi: 10.1038/276829a0. [DOI] [PubMed] [Google Scholar]
  2. Bennink J. R., Doherty P. C. Reciprocal stimulation of negatively selected high-responder and low-responder T cells in virus-infected recipients. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3482–3485. doi: 10.1073/pnas.76.7.3482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bevan M. J., Fink P. J. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978;42:3–19. doi: 10.1111/j.1600-065x.1978.tb00256.x. [DOI] [PubMed] [Google Scholar]
  5. Billings P., Burakoff S. J., Dorf M. E., Benacerraf B. Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. J Exp Med. 1978 Aug 1;148(2):352–359. doi: 10.1084/jem.148.2.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blanden R. V., Andrew M. E. Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type. J Exp Med. 1979 Feb 1;149(2):535–538. doi: 10.1084/jem.149.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Corley R. B., Kindred B., Lefkovits I. Positive and negative allogeneic effects mediated by MLR-primed lymphocytes: quantitation by limiting dilution analysis. J Immunol. 1978 Sep;121(3):1082–1089. [PubMed] [Google Scholar]
  8. Doherty P. C., Bennink J. C. Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex. J Exp Med. 1979 Jan 1;149(1):150–157. doi: 10.1084/jem.149.1.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doherty P. C., Biddison W. E., Bennink J. R., Knowles B. B. Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype. J Exp Med. 1978 Aug 1;148(2):534–543. doi: 10.1084/jem.148.2.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Katz D. H. The allogeneic effect on immune responses: model for regulatory influences of T lymphocytes on the immune system. Transplant Rev. 1972;12:141–179. doi: 10.1111/j.1600-065x.1972.tb00055.x. [DOI] [PubMed] [Google Scholar]
  11. Matsunaga T., Simpson E. H-2 complementation in anti-H-Y cytotoxic T-cell responses can occur in chimeric mice. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6207–6210. doi: 10.1073/pnas.75.12.6207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Zinkernagel R. M., Althage A., Cooper S., Callahan G., Klein J. In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells. J Exp Med. 1978 Sep 1;148(3):805–810. doi: 10.1084/jem.148.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zinkernagel R. M., Althage A., Cooper S., Kreeb G., Klein P. A., Sefton B., Flaherty L., Stimpfling J., Shreffler D., Klein J. Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness. J Exp Med. 1978 Aug 1;148(2):592–606. doi: 10.1084/jem.148.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zinkernagel R. M., Althage A. Search for suppression of T cells specific for the second nonhost H-2 haplotype in F1 leads to P irradiation bone marrow chimeras. J Immunol. 1979 May;122(5):1742–1749. [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. von Boehmer H., Haas W., Jerne N. K. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. Proc Natl Acad Sci U S A. 1978 May;75(5):2439–2442. doi: 10.1073/pnas.75.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES