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. 1979 Sep 19;150(3):432–444. doi: 10.1084/jem.150.3.432

Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus

PMCID: PMC2185659  PMID: 113478

Abstract

In an attempt to produce allonatibodies to cytotoxic T-cell receptors, hyperimmune anti-lymphocyte antisera have been raised in mice of various strain combinations, and have been tested for their ability to block allogeneic cell-mediated lymphocytotoxicity (CML) in the absence of complement at the T killer cell level. Most of the sera failed to show any significant and reproducible inhibitory effects. However, among C3H anti-B10.BR antisera, some sera were found to be capable of significantly inhibiting CML. This effect was attributable to antibodies reacting with the killer population rather than the target cells, because the sera inhibited B10 anti-C3H CML but not C3H anti-b10 CML. Among mouse strains tested, A/J, BALB/c, B10, and B6 strains were sensitive to the inhibitory effect of the sera whereas AKR, CBA, C3H, and DBA/2 strains were insensitive. The sensitivity of killer cells to the inhibitory effect correlated well with the strain distribution of the Lyt-2.2 antigen. In the presence of complement, these same sera were toxic to 100% of spleen cells of AKR, BALB/c, B10, and DBA/2 strains, with comparable cytotoxic titers. Thus, the inhibitory activity of the sera could not be explained by nonspecific effects of high-titered antibodies. To study the relationship between the antigen(s) responsible for the blocking effect and Lyt-2-linked genes, killer cells from Lyt-2 congenic strains were tested and conventional anti-Lyt-2.2 antisera were raised in an appropriate congenic strain combination. Killer cells from B6, but not from B6.Ly2.1 animals, were significantly sensitive to the blocking effects of the inhibitory C3H anti-B10.BR sera. The conventional anti-Lyt.2.2 sera did produce CML blocking, although there was no apparent correlation between such blocking and the anti-Lyt-2.2 cytotoxic titer. These results thus indicate that the target molecules responsible for blocking of killer cells are encoded or regulated by genes that are closely linked to or identical with Lyt-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. Binz H., Wigzell H. Antigen-binding, idiotypic T-lymphocyte receptors. Contemp Top Immunobiol. 1977;7:113–177. doi: 10.1007/978-1-4684-3054-7_4. [DOI] [PubMed] [Google Scholar]
  2. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Cantor H., Shen F. W., Boyse E. A. Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1391–1340. doi: 10.1084/jem.143.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cerottini J. C., Nordin A. A., Brunner K. T. Cellular and humoral response to transplantation antigens. I. Development of alloantibody-forming cells and cytotoxic lymphocytes in the graft-versus-host reaction. J Exp Med. 1971 Aug 1;134(2):553–564. doi: 10.1084/jem.134.2.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dickler H. B., Kubicek M. T., Arbeit R. D., Sharrow S. O. Studies on the nature of the relationship between Ia antigens and Fc receptors on murine B lymphocytes. J Immunol. 1977 Jul;119(1):348–354. [PubMed] [Google Scholar]
  7. Gibson D. Genetic polymorphism of mouse immunoglobulin light chains revealed by isoelectric focusing. J Exp Med. 1976 Jul 1;144(1):298–303. doi: 10.1084/jem.144.1.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gottlieb P. D. Genetic correlation of a mouse light chain variable region marker with a thymocyte surface antigen. J Exp Med. 1974 Nov 1;140(5):1432–1437. doi: 10.1084/jem.140.5.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Huber B., Cantor H., Shen F. W., Boyse E. A. Independent differentiative pathways of Ly1 and Ly23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses. J Exp Med. 1976 Oct 1;144(4):1128–1133. doi: 10.1084/jem.144.4.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huber B., Devinsky O., Gershon R. K., Cantor H. Cell-mediated immunity: delayed-type hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1534–1539. doi: 10.1084/jem.143.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimura A. K. Inhibition of specific cell-mediated cytotoxicity by anti-T-cell receptor antibody. J Exp Med. 1974 Apr 1;139(4):888–901. doi: 10.1084/jem.139.4.888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimura A. K., Wigzell H. Cytotoxic T lymphocyte membrane components: an analysis of structures related to function. Contemp Top Mol Immunol. 1977;6:209–244. doi: 10.1007/978-1-4684-2841-4_7. [DOI] [PubMed] [Google Scholar]
  13. Krawinkel U., Cramer M., Imanishi-Kari T., Jack R. S., Rajewsky K., Mäkelä O. Isolated hapten-binding receptors of sensitized lymphocytes. I. Receptors from nylon wool-enriched mouse T lymphocytes lack serological markers of immunoglobulin constant domains but express heavy chain variable portions. Eur J Immunol. 1977 Aug;7(8):566–573. doi: 10.1002/eji.1830070814. [DOI] [PubMed] [Google Scholar]
  14. Nabholz M., Vives J., Young H. M., Meo T., Miggiano V., Rijnbeek A., Shreffler D. C. Cell-mediated cell lysis in vitro: genetic control of killer cell production and target specificities in the mouse. Eur J Immunol. 1974 May;4(5):378–387. doi: 10.1002/eji.1830040514. [DOI] [PubMed] [Google Scholar]
  15. Redelman D., Trefts P. E. In vitro studies of the rabbit immune system. VI. Rabbit anti-mouse cytotoxic T effector cells are inhibited by anti-rabbit T cell serum in the absence of complement. J Immunol. 1978 Oct;121(4):1532–1539. [PubMed] [Google Scholar]
  16. Sachs D. H., Winn H. J., Russell P. S. The immunologic response to xenografts. Recognition of mouse H-2 histocompatibility antigens by the rat. J Immunol. 1971 Aug;107(2):481–492. [PubMed] [Google Scholar]
  17. Shiku H., Kisielow P., Bean M. A., Takahashi T., Boyse E. A., Oettgen H. F., Old L. J. Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells. J Exp Med. 1975 Jan 1;141(1):227–241. doi: 10.1084/jem.141.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Warner N. L., Byrt P., Ada G. L. Blocking of the lymphocyte antigen receptor site with anti-immunoglobulin sera in vitro. Nature. 1970 Jun 6;226(5249):942–943. doi: 10.1038/226942a0. [DOI] [PubMed] [Google Scholar]
  19. 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]

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