Skip to main content
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
. 1993 May 1;90(9):3913–3917. doi: 10.1073/pnas.90.9.3913

Mice lacking major histocompatibility complex class I and class II molecules.

M J Grusby 1, H Auchincloss Jr 1, R Lee 1, R S Johnson 1, J P Spencer 1, M Zijlstra 1, R Jaenisch 1, V E Papaioannou 1, L H Glimcher 1
PMCID: PMC46416  PMID: 8483910

Abstract

Mice lacking major histocompatibility complex (MHC) antigens were generated by mating beta 2-microglobulin-deficient, and therefore class I-deficient, animals with MHC class II-deficient animals. When housed under sterile conditions, the resulting MHC-deficient mice appear healthy, survive for many months, and breed successfully. Phenotypically, MHC-deficient mice are depleted of CD4+ and CD8+ T cells in peripheral lymphoid organs due to a lack of appropriate restricting elements. In contrast, the B-cell compartment of these animals appears intact, and MHC-deficient mice can mount specific antibody responses when challenged with a T-independent antigen. Spleen cells from MHC-deficient animals are poor stimulators and responders in a mixed lymphocyte reaction. Despite their relatively weak cellular immune responses in vitro, MHC-deficient mice reject allogeneic skin grafts with little delay, and grafts from MHC-deficient animals are rapidly rejected by normal allogeneic recipients. Taken together, these results emphasize the plasticity of the immune system and suggest that MHC-deficient mice may be useful for examining compensatory mechanisms in severely immunocompromised animals.

Full text

PDF
3913

Selected References

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

  1. Allen H., Fraser J., Flyer D., Calvin S., Flavell R. Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7447–7451. doi: 10.1073/pnas.83.19.7447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Auchincloss H., Jr, Mayer T., Ghobrial R., Winn H. J. T-cell subsets, bm mutants, and the mechanisms of allogeneic skin graft rejection. Immunol Res. 1989;8(2):149–164. doi: 10.1007/BF02919076. [DOI] [PubMed] [Google Scholar]
  3. Bender B. S., Croghan T., Zhang L., Small P. A., Jr Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med. 1992 Apr 1;175(4):1143–1145. doi: 10.1084/jem.175.4.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bix M., Liao N. S., Zijlstra M., Loring J., Jaenisch R., Raulet D. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature. 1991 Jan 24;349(6307):329–331. doi: 10.1038/349329a0. [DOI] [PubMed] [Google Scholar]
  5. Bix M., Raulet D. Functionally conformed free class I heavy chains exist on the surface of beta 2 microglobulin negative cells. J Exp Med. 1992 Sep 1;176(3):829–834. doi: 10.1084/jem.176.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casper J. T., Ash R. A., Kirchner P., Hunter J. B., Havens P. L., Chusid M. J. Successful treatment with an unrelated-donor bone marrow transplant in an HLA-deficient patient with severe combined immune deficiency ("bare lymphocyte syndrome"). J Pediatr. 1990 Feb;116(2):262–265. doi: 10.1016/s0022-3476(05)82885-9. [DOI] [PubMed] [Google Scholar]
  7. Cosgrove D., Gray D., Dierich A., Kaufman J., Lemeur M., Benoist C., Mathis D. Mice lacking MHC class II molecules. Cell. 1991 Sep 6;66(5):1051–1066. doi: 10.1016/0092-8674(91)90448-8. [DOI] [PubMed] [Google Scholar]
  8. Eichelberger M., Allan W., Zijlstra M., Jaenisch R., Doherty P. C. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991 Oct 1;174(4):875–880. doi: 10.1084/jem.174.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
  10. Höglund P., Ohlén C., Carbone E., Franksson L., Ljunggren H. G., Latour A., Koller B., Kärre K. Recognition of beta 2-microglobulin-negative (beta 2m-) T-cell blasts by natural killer cells from normal but not from beta 2m- mice: nonresponsiveness controlled by beta 2m- bone marrow in chimeric mice. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10332–10336. doi: 10.1073/pnas.88.22.10332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  12. Liao N. S., Bix M., Zijlstra M., Jaenisch R., Raulet D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science. 1991 Jul 12;253(5016):199–202. doi: 10.1126/science.1853205. [DOI] [PubMed] [Google Scholar]
  13. Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
  14. Paul W. E. Cytokines. Poking holes in the network. Nature. 1992 May 7;357(6373):16–17. doi: 10.1038/357016a0. [DOI] [PubMed] [Google Scholar]
  15. Rajewsky K. A phenotype or not: targeting genes in the immune system. Science. 1992 Apr 24;256(5056):483–483. doi: 10.1126/science.1570513. [DOI] [PubMed] [Google Scholar]
  16. Shultz L. D., Sidman C. L. Genetically determined murine models of immunodeficiency. Annu Rev Immunol. 1987;5:367–403. doi: 10.1146/annurev.iy.05.040187.002055. [DOI] [PubMed] [Google Scholar]
  17. Spriggs M. K., Koller B. H., Sato T., Morrissey P. J., Fanslow W. C., Smithies O., Voice R. F., Widmer M. B., Maliszewski C. R. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6070–6074. doi: 10.1073/pnas.89.13.6070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tarleton R. L., Koller B. H., Latour A., Postan M. Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature. 1992 Mar 26;356(6367):338–340. doi: 10.1038/356338a0. [DOI] [PubMed] [Google Scholar]
  19. Zijlstra M., Auchincloss H., Jr, Loring J. M., Chase C. M., Russell P. S., Jaenisch R. Skin graft rejection by beta 2-microglobulin-deficient mice. J Exp Med. 1992 Apr 1;175(4):885–893. doi: 10.1084/jem.175.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zijlstra M., Bix M., Simister N. E., Loring J. M., Raulet D. H., Jaenisch R. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 1990 Apr 19;344(6268):742–746. doi: 10.1038/344742a0. [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