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.
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Selected References
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]