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. 1979 Jan 1;149(1):150–157. doi: 10.1084/jem.149.1.150

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

PMCID: PMC2184731  PMID: 310857

Abstract

BALB/c (H-2Kd-Dd) spleen and lymph node populations were specifically depleted of alloreactive potential by filtration through H-2 different, irradiated recipients. These negatively selected T cells were then stimulated with vaccinia virus in mice expressing the foreign H-2 determinants encountered previously in the filter environment. Strong virus-immune cytotoxic T-cell responses were seen in the context of H- 2Kk and H-2Ks, but not 2H-2Kb. The T cells generated were not cross- reactive for the H-2Kk and H-2Kd alleles, and responsiveness was independent of concurrent presence of effector populations operating at H-2D. These findings are consisent with the idea that recognition is mediated via a complex receptor, part of which is specific for virus and part for self H-2. The capacity to interact with allogeneic, virus- infected cells may then reflect aberrant recognition of a virus-H-2- antigen complex by this single, large binding site. For instance, the T cell which would normally recognize H-2Kd-virus x, or H-2Dd-minor histocompatibility antigen Z, may now show specificity for H-2Kk- vaccinia virus. Implications for both the selective role of the thymus and for mechanisms of tolerance are discussed.

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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. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  2. 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]
  3. Binz H., Frischkencht H., Mercolli C., Wigzell H. Partial characterization of cell surface idiotypes on alloantigen-activated T lymphoblasts. Scand J Immunol. 1978;7(6):481–485. doi: 10.1111/j.1365-3083.1978.tb00481.x. [DOI] [PubMed] [Google Scholar]
  4. Bourguignon L. Y., Hyman R., Trowbridge I., Singer S. J. Participation of histocompatibility antigens in capping of molecularly independent cell surface components by their specific antibodies. Proc Natl Acad Sci U S A. 1978 May;75(5):2406–2410. doi: 10.1073/pnas.75.5.2406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bubbers J. E., Lilly F. Selective incorporation of H-2 antigenic determinants into Friend virus particles. Nature. 1977 Mar 31;266(5601):458–459. doi: 10.1038/266458a0. [DOI] [PubMed] [Google Scholar]
  6. Cancro M. P., Gerhard W., Klinman N. R. The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. J Exp Med. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
  9. Krammer P. H., Eichmann K. T cell receptor idiotypes are controlled by genes in the heavy chain linkage group and the major histocompatibility complex. Nature. 1977 Dec 22;270(5639):733–735. doi: 10.1038/270733a0. [DOI] [PubMed] [Google Scholar]
  10. Schrader J. W., Cunningham B. A., Edelman G. M. Functional interactions of viral and histocompatibility antigens at tumor cell surfaces. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5066–5070. doi: 10.1073/pnas.72.12.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shearer G. M., Schmitt-Verhulst A. M. Major histocompatibility complex restricted cell-mediated immunity. Adv Immunol. 1977;25:55–91. doi: 10.1016/s0065-2776(08)60931-1. [DOI] [PubMed] [Google Scholar]
  12. Wilson D. B., Lindahl K. F., Wilson D. H., Sprent J. The generation of killer cells to trinitrophenyl-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens. J Exp Med. 1977 Aug 1;146(2):361–367. doi: 10.1084/jem.146.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. 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]
  16. Zinkernagel R. M., Callahan G. N., Klein J., Dennert G. Cytotoxic T cells learn specificity for self H-2 during differentiation in the thymus. Nature. 1978 Jan 19;271(5642):251–253. doi: 10.1038/271251a0. [DOI] [PubMed] [Google Scholar]
  17. Zinkernagel R. M., Doherty P. C. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature. 1974 Oct 11;251(5475):547–548. doi: 10.1038/251547a0. [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]

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