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. 1978 Sep 1;148(3):805–810. doi: 10.1084/jem.148.3.805

In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells

RM Zinkernagel, A Althage, S Cooper, G Callahan, J Klein
PMCID: PMC2184993  PMID: 100570

Abstract

The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) × K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell’s Ir genotype, and that thymic selection of a T cell’s restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell’s/r phenotype.

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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. 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]
  3. Doherty P. C., Zinkernagel R. M. A biological role for the major histocompatibility antigens. Lancet. 1975 Jun 28;1(7922):1406–1409. doi: 10.1016/s0140-6736(75)92610-0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Paul W. E., Benacerraf B. Functional specificity of thymus- dependent lymphocytes. Science. 1977 Mar 25;195(4284):1293–1300. doi: 10.1126/science.320663. [DOI] [PubMed] [Google Scholar]
  6. Press J. L., McDevitt H. O. Allotype-specific analysis of anti-(Tyr,Glu)-Ala-Lys antibodies produced by Ir-1A high and low responder chimeric mice. J Exp Med. 1977 Dec 1;146(6):1815–1820. doi: 10.1084/jem.146.6.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. 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]

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