Letter | Published:

Functional expression of a microinjected Edα gene in C57BL/6 transgenic mice

Abstract

The class II major histocompatibility antigens, I–A and I–E, have been detected on the surface of certain immunocompetent cells, including B lymphocytes and monocytes1–3. These molecules are involved in cell–cell interactions in the immune responses4,5. Each class II antigen consists of two subunits, α and β chains, and the genes encoding these subunits have been well characterized at the molecular level6–9. To analyse the regulatory mechanism of gene expression and the role of the I–E antigen in the regulation of the immune responses, we have produced transgenic mice by microinjecting cloned Edα genes into fertilized eggs of C57BL/6 mice of b haplotype. This strain of mouse carries a deletion in the upstream (5′) region of the gene covering the transcriptional promoter and, therefore, does not express this gene10. Interestingly, this genetic defect of the gene is accompanied by the inability of the host mouse to respond to a certain set of antigens, phenomena generally termed Ir gene control11,12. We report here that the Edα genes are expressed in these transgenic mice to form the I–EdαEdβ antigen on the surface of B lymphocytes and monocytes and that these I–E antigens are functional in terms of the induction of a mixed lymphocyte reaction and the restoration of immune responsiveness to poly(L-glutamic acid-L-lysine-L-phenylalanine) (GL-Phe).

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hammerling, G., Deak, B., Mauve, G., Hammerling, U. & McDevitt, H. O. Immunogenetics 1, 68–74 (1974).

  2. 2

    Steeg, P., Moore, R. & Oppenheim, J. J. exp. Med. 152, 1734–1744 (1980).

  3. 3

    Snyder, D. S., Beller, D. I. & Unanue, E. R. Nature 299, 164–165 (1982).

  4. 4

    McDevitt, H. O. J. Immunogenet. 8, 287–295 (1983).

  5. 5

    Klein, J., Juretic, A., Baxevanis, C. N. & Nagy, Z. A. Nature 291, 455–460 (1981).

  6. 6

    Steinmetz, M. et al. Nature 300, 35–43 (1982).

  7. 7

    Hyldig-Nielsen, J. J. et al. Nucleic Acids Res. 11, 5055–5071 (1983).

  8. 8

    Mathis, D. J., Benoist, C. O., Williams, V. E. II, Kanter, M. R. & McDevitt, H. O. Cell 32, 745–754 (1983).

  9. 9

    Saito, H., Maki, R. A., Clayton, L. K. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 80, 5520–5524 (1983).

  10. 10

    Mathis, D. J., Benoist, C., Williams, V. E. II, Kanter, M. R. & McDevitt, H. O. Proc. natn. Acad. Sci. U.S.A. 80, 273–277 (1983).

  11. 11

    Benacerraf, B., Green, I. & Paula, W. E. Cold Spring Harb. Symp. quant. Biol. 32, 569–576 (1967).

  12. 12

    McDevitt, H. O. & Sela, M. J exp. Med. 126, 969–981 (1967).

  13. 13

    Lerner, E. A. et al. J. exp. Med. 152, 1085–1101 (1980).

  14. 14

    Hammerling, G. J. Transplantn Rev. 30, 64–82. (1976).

  15. 15

    Wiman, K. et al. Nature 276, 711–713 (1978).

  16. 16

    Natali, P. G. et al. Transplantation 31, 75–78 (1981).

  17. 17

    Hirschberg, H., Vergh, O. J. & Thorsby, E. J. exp. Med. 152, 249s–255s (1980).

  18. 18

    Lacy, E., Roberts, S., Evans, E. P., Burtenshaw, M. S. & Costantini, F. D. Cell 34, 343–358 (1983).

  19. 19

    Grosschedl, R., Weaver, D., Baltimore, D. & Costantini, F. Cell 36, 647–658 (1984).

  20. 20

    Benacerraf, B. & Dorf, M. E. Cold Spring Harb. Symp. quant. Biol. 41, 465–467 (1976).

  21. 21

    Schwartz, R. H., David, C. S., Sachs, D. H. & Paul, W. E. J. Immun. 117, 531–540 (1976).

  22. 22

    Goodenow, R. S. et al. Science 215, 677–679 (1982).

  23. 23

    Dorf, M. E. & Benacerraf, B. Proc. natn. Acad. Sci. U.S.A. 72, 3671–3675 (1976).

  24. 24

    Solinger, A. M., Ulter, M. E., Malgoltash, E. & Schwartz, R. H. J. exp. Med. 150, 830–848 (1979).

  25. 25

    Rabourdin-Combe, C. & Mach, B. Nature 303, 670–674 (1983).

  26. 26

    Mallisen, B., Steinmetz, M., McMillan, M., Pierres, M. & Hood, L. Nature 305, 440–443 (1983).

  27. 27

    Mellor, A. L. et al. Nature 298, 529–534 (1982).

  28. 28

    Margulies, D. H., Evans, G. A., Ozato, K. & Seidman, J. G. J. Immun. 130, 463–470 (1983).

  29. 29

    Germain, R. N., Norcross, M. A. & Margulies, D. H. Nature 306, 190–194 (1983).

  30. 30

    Folsom, V. et al. Proc. natn. Acad. Sci. U.S.A. 81, 2045–2049 (1984).

  31. 31

    Corradin, G. & Chiller, J. M. J. exp. Med. 149, 436–447 (1979).

  32. 32

    Southern, E. J. molec. Biol. 98, 503 (1975).

  33. 33

    Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.