Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1976 Sep 1;144(3):776–787. doi: 10.1084/jem.144.3.776

H-2 restriction of virus-specific T-cell-mediated effector functions in vivo. II. Adoptive transfer of delayed-type hypersensitivity to murine lymphocytic choriomeningits virus is restriced by the K and D region of H-2

PMCID: PMC2190399  PMID: 1085340

Abstract

In mice, primary footpad swelling after local infection with lymphocytic choriomeningitis virus (LCMV) and delayed-type hypersensitivity (DTH) adoptively transferred by LCMV immune lymphocytes are T-cell dependent. Nude mice do not develop primary footpad swelling, and T-cell depletion abrogates the capacity to transfer LCMV-specific DTH. Effector T cells involved in eliciting dose- dependent DTH are virus specific in that vaccinia virus-immune lymphocytes could not elicit DTH in LCMV-infected mice. The adoptive transfer of DTH is restricted to H-2K or H-2D compatible donor- recipient combinations. Distinct from the fowl-gamma-globulin DTH model, I-region compatibility is neither necessary nor alone sufficient. Whatever the mechanisms involved in this K- or D-region associated restriction in vivo, it most likely operates at the level of T-cell recognition of "altered self" coded in K or D. T cells associated with the I region (helper T cells and DTH-T cells to fowl- gamma-globulin) are specific for soluble, defined, and inert antigens. T cells associated with the K and D region (T cells cytotoxic in vitro and in vivo for acute LCMV-infected cells, DTH effector T cells, and anti-viral T cells) are specific for infectious, multiplying virus. The fact that T-cell specificity is differentially linked with the I region or with the K and D regions of H-2 may reflect the fundamental biological differences of these antigens. Although it cannot be excluded that separate functional subclasses of T-effector cells could have self-recognizers for different cell surface structures coded in I or K and D, it is more likely that the antigen parameters determine whether T cells are specific for "altered" I or "altered" K- or D-coded structures.

Full Text

The Full Text of this article is available as a PDF (696.8 KB).

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. 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., Hapel A. J., Jackson D. C. Mode of action of Ir genes and the nature of T cell receptors for antigen. Immunochemistry. 1976 Feb;13(2):179–191. doi: 10.1016/0019-2791(76)90287-1. [DOI] [PubMed] [Google Scholar]
  4. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. II. Passive transfer of recovery mechanisms with immune lymphoid cells. J Exp Med. 1971 May 1;133(5):1074–1089. doi: 10.1084/jem.133.5.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [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. Crowle A. J. Delayed hypersensitivity in the mouse. Adv Immunol. 1975;20:197–264. doi: 10.1016/s0065-2776(08)60209-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Doherty P. C., Dunlop M. B., Parish C. R., Zinkernagel R. M. Inflammatory process in murine lymphocytic choriomeningitis is maximal in H-2K or H-2D compatible interactions. J Immunol. 1976 Jul;117(1):187–190. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Dvorak H. F., Simpson B. A., Flax M. H., Leskowitz S. The fate of antigen in delayed hypersensitivity skin reactions. J Immunol. 1970 Mar;104(3):718–727. [PubMed] [Google Scholar]
  14. Erb P., Feldmann M. The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens. J Exp Med. 1975 Aug 1;142(2):460–472. doi: 10.1084/jem.142.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garrido F., Schirrmacher V., Festenstein H. H-2-like specificities of foreign haplotypes appearing on a mouse sarcoma after vaccinia virus infection. Nature. 1976 Jan 22;259(5540):228–230. doi: 10.1038/259228a0. [DOI] [PubMed] [Google Scholar]
  16. HOTCHIN J., BENSON L. THE PATHOGENESIS OF LYMPHOCYTIC CHORIOMENINGITIS IN MICE: THE EFFECTS OF DIFFERENT INOCULATION ROUTES AND THE FOOTPAD RESPONSE. J Immunol. 1963 Oct;91:460–468. [PubMed] [Google Scholar]
  17. Heber-Katz E., Wilson D. B. Collaboration of allogeneic T and B lymphocytes in the primary antibody response to sheep erythrocytes in vitro. J Exp Med. 1975 Oct 1;142(4):928–935. doi: 10.1084/jem.142.4.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz D. H., Benacerraf B. The function and interrelationships of T-cell receptors, Ir genes and other histocompatibility gene products. Transplant Rev. 1975;22:175–195. doi: 10.1111/j.1600-065x.1975.tb01559.x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. 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]
  22. Mackaness G. B., Lagrange P. H., Ishibashi T. The modifying effect of BCG on the immunological induction of T cells. J Exp Med. 1974 Jun 1;139(6):1540–1552. doi: 10.1084/jem.139.6.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Pfizenmaier K., Strazinski-Powitz A., Rodt H., Röllinghoff M., Wagner H. Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells. J Exp Med. 1976 Apr 1;143(4):999–1004. doi: 10.1084/jem.143.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Tosolini F. A., Mims C. A. Effect of murine strain and viral strain on the pathogenesis of lymphocytic choriomeningitis infection and a study of footpad responses. J Infect Dis. 1971 Feb;123(2):134–144. doi: 10.1093/infdis/123.2.134. [DOI] [PubMed] [Google Scholar]
  28. 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]
  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. Zinkernagel R. M. Restriction by H-2 gene complex of transfer of cell-mediated immunity to Listeria monocytogenes. Nature. 1974 Sep 20;251(5472):230–233. doi: 10.1038/251230a0. [DOI] [PubMed] [Google Scholar]
  32. Zinkernagel R. M. Virus-specific T-cell-mediated cytotoxicity across the H-2 barrier to virus-altered alloantigen. Nature. 1976 May 13;261(5556):139–141. doi: 10.1038/261139a0. [DOI] [PubMed] [Google Scholar]
  33. 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]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES