Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Mar;87(5):1762–1766. doi: 10.1073/pnas.87.5.1762

Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen.

B Arnold 1, M Messerle 1, L Jatsch 1, G Küblbeck 1, U Koszinowski 1
PMCID: PMC53563  PMID: 2308936

Abstract

The properties of transmembrane and soluble transplantation antigens were compared with respect to the induction of tolerance and the selection of the T-cell repertoire. For this purpose, transgenic (H-2b x H-2d)F1 mice were constructed that carry integrated copies of a modified H-2Kk gene resulting in the secretion from various cell types including thymocytes of soluble H-2Kk molecules. Despite the presence of H-2Kk antigen, these mice were still able to generate an H-2Kk-specific T-cell response. This response was comparable to that produced by normal littermates when stimulated with cells expressing membrane H-2Kk in a mixed lymphocyte reaction. In contrast, only transgenic mice failed to generate a cytolytic T-cell response to soluble H-2Kk antigen expressed by recombinant vaccinia virus and presented by the H-2Db molecule. These data imply the presence of two populations of alloreactive cytolytic T cells. A small fraction of T cells recognizes alloantigen as antigenic peptide(s) presented by other major histocompatibility complex class I molecules and tolerance can be induced in this population by soluble alloantigen. The majority of T cells, however, require the whole cell membrane-expressed class I molecule for recognition. This population is not affected by tolerance induction to the soluble major histocompatibility complex class I molecule.

Full text

PDF
1762

Images in this article

1763Image
on p.1763

Selected References

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

  1. Allen H., Wraith D., Pala P., Askonas B., Flavell R. A. Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites. Nature. 1984 May 17;309(5965):279–281. doi: 10.1038/309279a0. [DOI] [PubMed] [Google Scholar]
  2. Allison J., Campbell I. L., Morahan G., Mandel T. E., Harrison L. C., Miller J. F. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells. Nature. 1988 Jun 9;333(6173):529–533. doi: 10.1038/333529a0. [DOI] [PubMed] [Google Scholar]
  3. Arnold B., Burgert H. G., Hamann U., Hämmerling G., Kees U., Kvist S. Cytolytic T cells recognize the two amino-terminal domains of H-2 K antigens in tandem in influenza A infected cells. Cell. 1984 Aug;38(1):79–87. doi: 10.1016/0092-8674(84)90528-2. [DOI] [PubMed] [Google Scholar]
  4. Arnold B., Dill O., Küblbeck G., Jatsch L., Simon M. M., Tucker J., Hämmerling G. J. Alloreactive immune responses of transgenic mice expressing a foreign transplantation antigen in a soluble form. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2269–2273. doi: 10.1073/pnas.85.7.2269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arnold B., Horstmann U., Kuon W., Burgert H. G., Hämmerling G. J., Kvist S. Alloreactive cytolytic T-cell clones preferentially recognize conformational determinants on histocompatibility antigens: analysis with genetically engineered hybrid antigens. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7030–7034. doi: 10.1073/pnas.82.20.7030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  7. Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
  8. Coupar B. E., Andrew M. E., Boyle D. B., Blanden R. V. Immune responses to H-2Kd antigen expressed by recombinant vaccinia virus. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7879–7882. doi: 10.1073/pnas.83.20.7879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cranage M. P., Kouzarides T., Bankier A. T., Satchwell S., Weston K., Tomlinson P., Barrell B., Hart H., Bell S. E., Minson A. C. Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO J. 1986 Nov;5(11):3057–3063. doi: 10.1002/j.1460-2075.1986.tb04606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Drillien R., Spehner D. Physical mapping of vaccinia virus temperature-sensitive mutations. Virology. 1983 Dec;131(2):385–393. doi: 10.1016/0042-6822(83)90506-8. [DOI] [PubMed] [Google Scholar]
  11. Heath W. R., Hurd M. E., Carbone F. R., Sherman L. A. Peptide-dependent recognition of H-2Kb by alloreactive cytotoxic T lymphocytes. Nature. 1989 Oct 26;341(6244):749–752. doi: 10.1038/341749a0. [DOI] [PubMed] [Google Scholar]
  12. Koch S., Koch N., Robinson P., Hämmerling G. Comparison of allogeneic and xenogeneic determinants on the H-2Kk molecule. Transplantation. 1983 Aug;36(2):177–180. doi: 10.1097/00007890-198308000-00013. [DOI] [PubMed] [Google Scholar]
  13. Machy P., Arnold B., Aliño S., Leserman L. D. Interferon sensitive and insensitive MHC variants of a murine thymoma differentially resistant to methotrexate-containing antibody-directed liposomes and immunotoxin. J Immunol. 1986 Apr 15;136(8):3110–3115. [PubMed] [Google Scholar]
  14. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maryanski J. L., Pala P., Corradin G., Jordan B. R., Cerottini J. C. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide. Nature. 1986 Dec 11;324(6097):578–579. doi: 10.1038/324578a0. [DOI] [PubMed] [Google Scholar]
  16. Morahan G., Brennan F. E., Bhathal P. S., Allison J., Cox K. O., Miller J. F. Expression in transgenic mice of class I histocompatibility antigens controlled by the metallothionein promoter. Proc Natl Acad Sci U S A. 1989 May;86(10):3782–3786. doi: 10.1073/pnas.86.10.3782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Olson C. A., Williams L. C., McLaughlin-Taylor E., McMillan M. Creation of H-2 class I epitopes using synthetic peptides: recognition by alloreactive cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1031–1035. doi: 10.1073/pnas.86.3.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Parham P., Clayberger C., Zorn S. L., Ludwig D. S., Schoolnik G. K., Krensky A. M. Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the alpha 2 domain of HLA-A2. Nature. 1987 Feb 12;325(6105):625–628. doi: 10.1038/325625a0. [DOI] [PubMed] [Google Scholar]
  19. Schneck J., Maloy W. L., Coligan J. E., Margulies D. H. Inhibition of an allospecific T cell hybridoma by soluble class I proteins and peptides: estimation of the affinity of a T cell receptor for MHC. Cell. 1989 Jan 13;56(1):47–55. doi: 10.1016/0092-8674(89)90982-3. [DOI] [PubMed] [Google Scholar]
  20. Song E. S., Linsk R., Olson C. A., McMillan M., Goodenow R. S. Allospecific cytotoxic T lymphocytes recognize an H-2 peptide in the context of a murine major histocompatibility complex class I molecule. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1927–1931. doi: 10.1073/pnas.85.6.1927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  22. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES