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. 1976 Aug 1;144(2):519–532. doi: 10.1084/jem.144.2.519

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

PMCID: PMC2190371  PMID: 1085331

Abstract

Lymphocytic choriomeningitis virus (LCMV) and ectromelia virus-specific T-cell-mediated cytotoxicity was assayed in various strain combinations using as targets peritoneal macrophages which have been shown to express Ia antigens. Virus-specific cytotoxicity was found only in H-2K- or D-region compatible combinations. I-region compatibility was not necessary nor alone sufficient for lysis. Six different I-region specificities had no obvious effect on the capacity to generate in vivo specific cytotoxicity (expressed in vitro) associated with Dd. Low LCMV- specific cytotoxic activity generated in DBA/2 mice was caused by the non-H-2 genetic background. This trait was inversely related to the infectious virus dose and recessive. Non-H-2 genes, possibly involved in controlling initial spread and multiplication of virus, seem to be, at least in the examples tested, more important in determining virus- specific cytotoxic T-cell activity in spleens than are Ir genes coded in H-2.

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Selected References

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

  1. Bechtol K. B., Freed J. H., Herzenberg L. A., McDevitt H. O. Genetic control of the antibody response to poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys in C3H--CWB tetraparental mice. J Exp Med. 1974 Dec 1;140(6):1660–1675. doi: 10.1084/jem.140.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benacerraf B., McDevitt H. O. Histocompatibility-linked immune response genes. Science. 1972 Jan 21;175(4019):273–279. doi: 10.1126/science.175.4019.273. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Brem H., Folkman J. Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med. 1975 Feb 1;141(2):427–439. doi: 10.1084/jem.141.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bretscher P. A. On the control between cell-mediated, IgM and IgG immunity. Cell Immunol. 1974 Aug;13(2):171–195. doi: 10.1016/0008-8749(74)90237-8. [DOI] [PubMed] [Google Scholar]
  6. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  7. Cole G. A., Nathanson N. Lymphocytic choriomeningitis. Pathogenesis. Prog Med Virol. 1974;18(0):94–110. [PubMed] [Google Scholar]
  8. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  9. Doherty P. C., Zinkernagel R. M. H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J Exp Med. 1975 Feb 1;141(2):502–507. doi: 10.1084/jem.141.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Doherty P. C., Zinkernagel R. M., Ramshaw I. A. Specificity and development of cytotoxic thymus-derived lymphocytes in lymphocytic choriomeningitis. J Immunol. 1974 Apr;112(4):1548–1552. [PubMed] [Google Scholar]
  11. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  12. Dorf M. E., Dunham E. K., Johnson J. P., Benacerraf B. Genetic control of the immune response: the effect of non-H-2 linked genes on antibody production. J Immunol. 1974 Apr;112(4):1329–1336. [PubMed] [Google Scholar]
  13. 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]
  14. Katz D. H., Graves M., Dorf M. E., Dimuzio H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J Exp Med. 1975 Jan 1;141(1):263–268. doi: 10.1084/jem.141.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Kindred B., Shreffler D. C. H-2 dependence of co-operation between T and B cells in vivo. J Immunol. 1972 Nov;109(5):940–943. [PubMed] [Google Scholar]
  17. Koszinowski U., Ertl H. Lysis mediated by T cells and restricted by H-2 antigen of target cells infected with vaccinia virus. Nature. 1975 Jun 12;255(5509):552–554. doi: 10.1038/255552a0. [DOI] [PubMed] [Google Scholar]
  18. Marker O., Volkert M. Studies on cell-mediated immunity to lymphocytic choriomeningitis virus in mice. J Exp Med. 1973 Jun 1;137(6):1511–1525. doi: 10.1084/jem.137.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5095–5098. doi: 10.1073/pnas.72.12.5095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mozes E., McDevitt H. O., Jaton J. C., Sela M. The nature of the antigenic determinant in a genetic control of the antibody response. J Exp Med. 1969 Sep 1;130(3):493–504. doi: 10.1084/jem.130.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oldstone M. B., Dixon F. J., Mitchell G. F., McDevitt H. O. Histocompatibility-linked genetic control of disease susceptibility. Murine lymphocytic choriomeningitis virus infection. J Exp Med. 1973 May 1;137(5):1201–1212. doi: 10.1084/jem.137.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oldstone M. B., Dixon F. J. Tissue injury in lymphocytic choriomeningitis viral infection: virus-induced immunologically specific release of a cytotoxic factor from immune lymphoid cells. Virology. 1970 Dec;42(4):805–813. doi: 10.1016/0042-6822(70)90330-2. [DOI] [PubMed] [Google Scholar]
  23. Ralph P., Prichard J., Cohn M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol. 1975 Feb;114(2 Pt 2):898–905. [PubMed] [Google Scholar]
  24. Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]
  25. Silver D. M., McKenzie I. F., Winn H. J. Variations in the responses of C57BL-10J and A-J mice to sheep red blood cells. J Exp Med. 1972 Nov 1;136(5):1063–1071. doi: 10.1084/jem.136.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Unanue E. R., Dorf M. E., David C. S., Benacerraf B. The presence of I-region-associated antigens on B cells in molecules distinct from immunoglobulin and H-2K and H-2D. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5014–5016. doi: 10.1073/pnas.71.12.5014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zinkernagel R. M., Doherty P. C. Characteristics of the interaction in vitro between cytotoxic thymus-derived lymphocytes and target monolayers infected with lymphocytic choriomeningitis virus. Scand J Immunol. 1974;3(3):287–294. doi: 10.1111/j.1365-3083.1974.tb01259.x. [DOI] [PubMed] [Google Scholar]
  28. Zinkernagel R. M., Doherty P. C. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J Exp Med. 1973 Nov 1;138(5):1266–1269. doi: 10.1084/jem.138.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. von Boehmer H., Hudson L., Sprent J. Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras. J Exp Med. 1975 Oct 1;142(4):989–997. doi: 10.1084/jem.142.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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