Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Apr 1;157(4):1324–1338. doi: 10.1084/jem.157.4.1324

Neonatal tolerance of major histocompatibility complex antigens alters Ir gene control of the cytotoxic T cell response to vaccinia virus

PMCID: PMC2186975  PMID: 6220111

Abstract

The K region of H-2 controls the Tc cell response to vaccinia-Db. The Kb, Kd, and Kq alleles allow good Tc cell responses against vaccinia- Db. In contrast, the presence of Kk in H-2 recombinants 2R (Kk,Db) and 4R (Kk,Db) or in F1 hybrids greatly reduces the anti-vaccinia-Db response. The defect does not lie in antigen presentation, as infected 4R cells can stimulate anti-vaccinia-Db Tc cells in vitro. Furthermore, nonresponder animals possess Tc cell precursors for vaccinia-Db, as transfer of F1 nonresponder spleen cells into infected, lethally irradiated responder recipients allowed generation of anti-vaccinia-Db effector Tc cells. Secondary responses to vaccinia-Db can also be obtained in vitro from T cells of 4R animals. Feedback inhibition was excluded in experiments with mixed chimeras in which Kk and Db were expressed on separate cell populations. Neonatal tolerance of B10 animals to Kk suppressed the anti-vaccinia-Db response but did not affect anti-vaccinia-Kb, anti-lymphocytic choriomeningitis virus, or anti-H-2d responses. In cold target competition experiments, H-2k competitors inhibited vaccinia-Db-specific target cell lysis by Tc cells, which suggests that anti-vaccinia-Db and anti-H-2Kk Tc cells may cross-react. Therefore, we propose that the suppressive influence of Kk on anti-vaccinia-Db Tc cell responses is a consequence of self- tolerance and that suppression of anti-Kk Tc cells results in cross- reactive suppression of anti-vaccinia-Db Tc cells.

Full Text

The Full Text of this article is available as a PDF (1,020.8 KB).

Selected References

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

  1. Benacerraf B., Germain R. N. The immune response genes of the major histocompatibility complex. Immunol Rev. 1978;38:70–119. doi: 10.1111/j.1600-065x.1978.tb00385.x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Blanden R. V., McKenzie I. F., Kees U., Melvold R. W., Kohn H. I. Cytotoxic T-cell response to Ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2db mutation. J Exp Med. 1977 Sep 1;146(3):869–880. doi: 10.1084/jem.146.3.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Gardner I. D., Blanden R. V. The cell-mediated immune response to ectromelia virus infection. II. Secondary response in vitro and kinetics of memory T cell production in vivo. Cell Immunol. 1976 Mar 15;22(2):283–296. doi: 10.1016/0008-8749(76)90030-7. [DOI] [PubMed] [Google Scholar]
  6. Gardner I., Bowern N. A., Blanden R. V. Cell-mediated cytotoxicity against ectromelia virus-infected target cells. I. Specificity and kinetics. Eur J Immunol. 1974 Feb;4(2):63–67. doi: 10.1002/eji.1830040202. [DOI] [PubMed] [Google Scholar]
  7. Langman R. E. Cell-mediated immunity and the major histocompatibility complex. Rev Physiol Biochem Pharmacol. 1978;81:1–37. doi: 10.1007/BFb0034090. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Mullbacher A., Blanden R. V. H-2-linked control of cytotoxic T-cell responsiveness to alphavirus infection. Presence of H-2Dk during differentiation and stimulation converts stem cells of low responder genotype to T cells of responder phenotype. J Exp Med. 1979 Mar 1;149(3):786–790. doi: 10.1084/jem.149.3.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Müllbacher A., Blanden R. V. Cross-reactivity patterns of murine cytotoxic T lymphocytes. Cell Immunol. 1979 Mar 1;43(1):70–81. doi: 10.1016/0008-8749(79)90151-5. [DOI] [PubMed] [Google Scholar]
  11. Müllbacher A., Sheena J. H., Fierz W., Brenan M. Specific haplotype preference in congenic F1 hybrid mice in the cytotoxic T cell response to the male specific antigen H-Y. J Immunol. 1981 Aug;127(2):686–689. [PubMed] [Google Scholar]
  12. Pang T., Blanden R. V. Regulation of the T-cell response to ectromelia virus infection. I. Feedback suppression by effector T cells. J Exp Med. 1976 Mar 1;143(3):469–481. doi: 10.1084/jem.143.3.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Snell G. D. The H-2 locus of the mouse: observations and speculations concerning its comparative genetics and its polymorphism. Folia Biol (Praha) 1968;14(5):335–358. [PubMed] [Google Scholar]
  15. 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]
  16. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  17. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [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