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. 1991 Apr 1;173(4):841–847. doi: 10.1084/jem.173.4.841

Generation of T cells with lytic specificity for atypical antigens. III. Priming F1 animals with antigen-bearing cells also having reactivity for host alloantigens allows for potent lytic T cell responses

PMCID: PMC2190802  PMID: 2007855

Abstract

Here, we explore the conditions required for generating two different highly potent F1 antiparental killer cell populations to unusual antigens in rats. The first, L/DA anti-DA, has lytic specificity for two antigen systems: MTA, a mitochondrial antigen expressed on DA and DA Lewis (L) target cells restricted by RT1A class I molecules; and H, an antigen that maps to the class I-like RT1C region and is present only on parental target cells from donors homozygous at the major histocompatibility complex. The second killer population is generated in the reciprocal DA/L anti-DA combination and has lytic specificity only for the H antigen system. We show that the killer cells are T cells, and that generation of these F1 cytotoxic T lymphocytes (CTL) requires an in vivo priming step in which it is essential that the inoculated parental cells bear the relevant target antigens and possess alloreactivity for F1 host antigens. The requirement for alloreactivity and antigen on the same priming cell population suggests that these potent lytic responses depend on a situation akin to a hapten-carrier effect that bypasses otherwise ineffective helper responses by the host to these unusual antigens. Restimulation of F1 lymphocytes in culture is also necessary, requiring the presence of antigen on irradiated lymphoblast stimulator cells, but alloreactivity to responder cell antigens is not necessary; normal, nonactivated lymph node cells are completely ineffective as stimulators. For effective lysis, the target cells need not possess the potential for alloreactivity to responder F1 CTL. We also demonstrate in a preliminary way additional antigen systems defined by killer populations raised with other F1 antiparental strain combinations.

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Selected References

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  1. Aldrich C. J., Rodgers J. R., Rich R. R. Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene, Qdm. Immunogenetics. 1988;28(5):334–344. doi: 10.1007/BF00364232. [DOI] [PubMed] [Google Scholar]
  2. Bennett M. Biology and genetics of hybrid resistance. Adv Immunol. 1987;41:333–445. doi: 10.1016/s0065-2776(08)60034-6. [DOI] [PubMed] [Google Scholar]
  3. Davies J. D., Wilson D. H., Butcher G. W., Wilson D. B. Generation of T cells with lytic specificity for atypical antigens. II. A novel antigen system in the rat dependent on homozygous expression of major histocompatibility complex genes of the class I-like RT1C region. J Exp Med. 1991 Apr 1;173(4):833–839. doi: 10.1084/jem.173.4.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies J. D., Wilson D. H., Hermel E., Lindahl K. F., Butcher G. W., Wilson D. B. Generation of T cells with lytic specificity for atypical antigens. I. A mitochondrial antigen in the rat. J Exp Med. 1991 Apr 1;173(4):823–832. doi: 10.1084/jem.173.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fischer Lindahl K., Hermel E., Loveland B. E., Richards S., Wang C. R., Yonekawa H. Molecular definition of a mitochondrially encoded mouse minor histocompatibility antigen. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):563–569. doi: 10.1101/sqb.1989.054.01.067. [DOI] [PubMed] [Google Scholar]
  6. Ford W. L., Atkins R. C. Specific unresponsiveness of recirculating lymphocytes ater exposure to histocompatibility antigen in F 1 hybrid rats. Nat New Biol. 1971 Dec 8;234(49):178–180. doi: 10.1038/newbio234178a0. [DOI] [PubMed] [Google Scholar]
  7. Gordon R. D., Simpson E., Samelson L. E. In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice. J Exp Med. 1975 Nov 1;142(5):1108–1120. doi: 10.1084/jem.142.5.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guerder S., Matzinger P. Activation versus tolerance: a decision made by T helper cells. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 2):799–805. doi: 10.1101/sqb.1989.054.01.093. [DOI] [PubMed] [Google Scholar]
  9. Günther E., Wurst W. Cytotoxic T lymphocytes of the rat are predominantly restricted by RT1.A and not RT1.C-determined major histocompatibility class I antigens. Immunogenetics. 1984;20(1):1–12. doi: 10.1007/BF00373442. [DOI] [PubMed] [Google Scholar]
  10. Hurwitz J. L., Coleclough C., Cebra J. J. CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody. Cell. 1980 Nov;22(2 Pt 2):349–359. doi: 10.1016/0092-8674(80)90345-1. [DOI] [PubMed] [Google Scholar]
  11. Hünig T., Wallny H. J., Hartley J. K., Lawetzky A., Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. doi: 10.1084/jem.169.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Keene J. A., Forman J. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes. J Exp Med. 1982 Mar 1;155(3):768–782. doi: 10.1084/jem.155.3.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimura H., Wilson D. B. Anti-idiotypic cytotoxic T cells in rats with graft-versus-host disease. 1984 Mar 29-Apr 4Nature. 308(5958):463–464. doi: 10.1038/308463a0. [DOI] [PubMed] [Google Scholar]
  14. Kosmatopoulos K., Algara D. S., Orbach-Arbouys S. Anti-receptor anti-MHC cytotoxic T lymphocytes: their role in the resistance to graft vs host reaction. J Immunol. 1987 Feb 15;138(4):1038–1041. [PubMed] [Google Scholar]
  15. Lindahl K. F., Hausmann B., Robinson P. J., Guénet J. L., Wharton D. C., Winking H. Mta, the maternally transmitted antigen, is determined jointly by the chromosomal Hmt and the extrachromosomal Mtf genes. J Exp Med. 1986 Feb 1;163(2):334–346. doi: 10.1084/jem.163.2.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Livingstone A. M., Powis S. J., Diamond A. G., Butcher G. W., Howard J. C. A trans-acting major histocompatibility complex-linked gene whose alleles determine gain and loss changes in the antigenic structure of a classical class I molecule. J Exp Med. 1989 Sep 1;170(3):777–795. doi: 10.1084/jem.170.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raulet D. H., Bevan M. J. Helper T cells for cytotoxic T lymphocytes need not be I region restricted. J Exp Med. 1982 Jun 1;155(6):1766–1784. doi: 10.1084/jem.155.6.1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shearer G. M., Cudkowicz G. Induction of F1 hybrid antiparent cytotoxic effector cells: an in vitro model for hemopoietic histoincompatibility. Science. 1975 Nov 28;190(4217):890–893. doi: 10.1126/science.1188368. [DOI] [PubMed] [Google Scholar]
  19. Shearer G. M., Garbarino C. A., Cudkowicz G. In vitro induction of F1 hybrid anti-parent cell-mediated cytotoxicity. J Immunol. 1976 Sep;117(3):754–759. [PubMed] [Google Scholar]
  20. Wilson D. B., Marshak A., Howard J. C. SPECIFIC positive and negative selection of rat lymphocytes reactive to strong histocompatibility antigens: activation with alloantigens in vitro and in vivo. J Immunol. 1976 Apr;116(4):1030–1040. [PubMed] [Google Scholar]

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