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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 Jan;87(1):235–239. doi: 10.1073/pnas.87.1.235

Self-tolerance to HLA focuses the response of immunized HLA-transgenic mice on production of antibody to precise polymorphic HLA alloantigens.

G J Hämmerling 1, J W Chamberlain 1, O Dill 1, S Y Yang 1, B Dupont 1, R Khan 1, R Chua 1, S M Weissman 1, U Hämmerling 1
PMCID: PMC53236  PMID: 2404277

Abstract

HLA class I-transgenic mice express HLA antigen on their tissues and establish self-tolerance to the expressed monomorphic and polymorphic determinants. When challenged with skin grafts and lymphoid cells of a second HLA-transgenic mouse expressing a different HLA molecule, a specific immune response is elicited that is focused on the determinants specified by the allelic HLA differences between donor and recipient transgenic mice. In the studies described, this has led to the production of a number of monoclonal antibodies with specificity for the HLA-Cw3 and HLA-B7 crossreactive groups of class I antigens. These results indicate that immunization of appropriate transgenic strains of mice with murine cells expressing a different HLA allelic transgene should permit the generation of monoclonal antibodies of narrow specificity against virtually any polymorphic epitope on HLA antigens.

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Selected References

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

  1. 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]
  2. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  3. Boyse E. A., Miyazawa M., Aoki T., Old L. J. Ly-A and Ly-B: two systems of lymphocyte isoantigens in the mouse. Proc R Soc Lond B Biol Sci. 1968 Jun 11;170(1019):175–193. doi: 10.1098/rspb.1968.0032. [DOI] [PubMed] [Google Scholar]
  4. Chamberlain J. W., Nolan J. A., Conrad P. J., Vasavada H. A., Vasavada H. H., Ploegh H. L., Ganguly S., Janeway C. A., Jr, Weissman S. M. Tissue-specific and cell surface expression of human major histocompatibility complex class I heavy (HLA-B7) and light (beta 2-microglobulin) chain genes in transgenic mice. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7690–7694. doi: 10.1073/pnas.85.20.7690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chamberlain J. W., Nolan J. A., Gromkowski S. H., Kelley K. A., Eisenstadt J. M., Herrup K., Janeway C. A., Jr, Weissman S. M. Cell surface expression and alloantigenic function of a human class I MHC heavy chain gene (HLA-B7) in transgenic mice. J Immunol. 1988 Feb 15;140(4):1285–1292. [PubMed] [Google Scholar]
  6. Colombani J., Lepage V., Kalil J. HLA monoclonal antibody registry: second listing. Tissue Antigens. 1983 Aug;22(2):97–106. doi: 10.1111/j.1399-0039.1983.tb01175.x. [DOI] [PubMed] [Google Scholar]
  7. Coppin H. L., Denny D. W., Jr, Weissman S. M., McDevitt H. O. HLA-B locus polymorphism: studies with a specific hybridization probe. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8614–8618. doi: 10.1073/pnas.82.24.8614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dill O., Kievits F., Koch S., Ivanyi P., Hämmerling G. J. Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5664–5668. doi: 10.1073/pnas.85.15.5664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodnow C. C., Crosbie J., Adelstein S., Lavoie T. B., Smith-Gill S. J., Brink R. A., Pritchard-Briscoe H., Wotherspoon J. S., Loblay R. H., Raphael K. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988 Aug 25;334(6184):676–682. doi: 10.1038/334676a0. [DOI] [PubMed] [Google Scholar]
  10. Gordon J. W., Ruddle F. H. Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. Methods Enzymol. 1983;101:411–433. doi: 10.1016/0076-6879(83)01031-9. [DOI] [PubMed] [Google Scholar]
  11. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  12. Lemonnier F. A., Le Bouteiller P. P., Malissen B., Golstein P., Malissen M., Mishal Z., Caillol D. H., Jordan B. R., Kourilsky F. M. Transformation of murine LMTK- cells with purified HLA class I genes. I. Modification of conformation of murine beta 2-microglobulin upon its association with HLA heavy chains. J Immunol. 1983 Mar;130(3):1432–1438. [PubMed] [Google Scholar]
  13. Nemazee D. A., Bürki K. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature. 1989 Feb 9;337(6207):562–566. doi: 10.1038/337562a0. [DOI] [PubMed] [Google Scholar]
  14. Parham P., Lomen C. E., Lawlor D. A., Ways J. P., Holmes N., Coppin H. L., Salter R. D., Wan A. M., Ennis P. D. Nature of polymorphism in HLA-A, -B, and -C molecules. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4005–4009. doi: 10.1073/pnas.85.11.4005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Salter R. D., Clayberger C., Lomen C. E., Krensky A. M., Parham P. In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I HLA molecule. J Exp Med. 1987 Jul 1;166(1):283–288. doi: 10.1084/jem.166.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]

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