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. 1977 Sep 1;146(3):869–880. doi: 10.1084/jem.146.3.869

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-2(db) mutation

RV Blanden, IFC McKenzie, U Kees, RW Melvold, HI Kohn
PMCID: PMC2180797  PMID: 70498

Abstract

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D’) bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D’) was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.

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Selected References

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

  1. Bevan M. J. Interaction antigens detected by cytotoxic T cells with the major histocompatibility complex as modifier. Nature. 1975 Jul 31;256(5516):419–421. doi: 10.1038/256419a0. [DOI] [PubMed] [Google Scholar]
  2. Blanden R. V., Doherty P. C., Dunlop M. B., Gardner I. D., Zinkernagel R. M., David C. S. Genes required for cytotoxicity against virus-infected target cells in K and D regions of H-2 complex. Nature. 1975 Mar 20;254(5497):269–270. doi: 10.1038/254269a0. [DOI] [PubMed] [Google Scholar]
  3. Blanden R. V., Gardner I. D. The cell-mediated immune response to ectromelia virus infection. I. Kinetics and characteristics of the primary effector T cell response in vivo. Cell Immunol. 1976 Mar 15;22(2):271–282. doi: 10.1016/0008-8749(76)90029-0. [DOI] [PubMed] [Google Scholar]
  4. Brown J. L., Nathenson S. G. Structural differences between parent and mutant H-2K glycoproteins from two H-2K gene mutants: b6.c-h-2ba (Hzl) and B6-H-2bd (M505). J Immunol. 1977 Jan;118(1):98–102. [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. Hansen T. H., Cullen S. E., Melvold R., Kohn H., Flaherty L., Sachs D. H. Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D. J Exp Med. 1977 Jun 1;145(6):1550–1558. doi: 10.1084/jem.145.6.1550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hansen T. H., Cullen S. E., Sachs D. H. Immunochemical evidence for an additional H-2 region closely linked to H-2D. J Exp Med. 1977 Feb 1;145(2):438–442. doi: 10.1084/jem.145.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hämmerling G. J., Black S. J., Berek C., Eichmann K., Rajewsky K. Idiotypic analysis of lymphocytes in vitro. II. Genetic control of T-helper cell responsiveness to anti-idiotypic antibody. J Exp Med. 1976 Apr 1;143(4):861–869. doi: 10.1084/jem.143.4.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Janeway C. A., Wigzell H., Binz H. Two different VH gene products make up the T-cell receptors. Scand J Immunol. 1976;5(9):993–1001. doi: 10.1111/j.1365-3083.1976.tb03051.x. [DOI] [PubMed] [Google Scholar]
  11. Kees U., Blanden R. V. A single genetic element in H-2K affects mouse T-cell antiviral function in poxvirus infection. J Exp Med. 1976 Feb 1;143(2):450–455. doi: 10.1084/jem.143.2.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Melvold RW Kohn H. I. Histocompatibility gene mutation rates: H-2 and non-H-2. Mutat Res. 1975 Mar;27(3):415–418. doi: 10.1016/0027-5107(75)90300-0. [DOI] [PubMed] [Google Scholar]
  13. Pang T., Blanden R. V. The cell-mediated immune response to ectromelia virus infection. Secondary response in vitro: specificity, nature of effector and responder cells and requirements for induction of antigenic changes in stimulator cells. Aust J Exp Biol Med Sci. 1976 Jun;54(3):253–264. [PubMed] [Google Scholar]
  14. Schrader J. W., Edelman G. M. Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex. J Exp Med. 1977 Mar 1;145(3):523–539. doi: 10.1084/jem.145.3.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Silver J., Hood L. Structure and evolution of transplantation antigens: partial amino-acid sequences of H-2K and H-2D alloantigens. Proc Natl Acad Sci U S A. 1976 Feb;73(2):599–603. doi: 10.1073/pnas.73.2.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Snell G. D., Démant P., Cherry M. Haemagglutination and cytotoxic studies of H-2. V. T-e anti-27, 28, 29 family of antibodies. Folia Biol (Praha) 1974;20(3):145–167. [PubMed] [Google Scholar]
  17. Terhorst C., Parham P., Mann D. L., Strominger J. L. Structure of HLA antigens: amino-acid and carbohydrate compositions and NH2-terminal sequences of four antigen preparations. Proc Natl Acad Sci U S A. 1976 Mar;73(3):910–914. doi: 10.1073/pnas.73.3.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Zinkernagel R. M., Dunlop M. B., Blanden R. V., Doherty P. C., Shreffler D. C. H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response. J Exp Med. 1976 Aug 1;144(2):519–532. doi: 10.1084/jem.144.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zinkernagel R. M. H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. The H-2K structure involved is coded by a single cistron defined by H-2Kb mutant mice. J Exp Med. 1976 Feb 1;143(2):437–443. doi: 10.1084/jem.143.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]

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