Letter | Published:

Genes encoding ligands for deletion of Vβ11 T cells cosegregate with mammary tumour virus genomes

Abstract

THE T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR α and β chains1. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histo-compatibility complex: some combinations result in positive selection, others in negative selection. Negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive T cells. A group of self-ligands involved in clonal deletion was identified because they, like exogenous superantigens2, were recognized by almost all T cells expressing particular TCR Vβ genes. Vβ17a T cells are deleted by a tissue-specific ligand3,4; Vβ6, V07, Vβ8.1 and Vβ9 T cells are deleted by the minor lymphocyte-stimulating (Mls) determinant Mls-la (refs 5–8); Vβ3 T cells by Mls-2a and Mls-3a (refs 9,10); Vβ11 T cells11 by ligands encoded by independently segregating genes; and Vβ5 T cells by ligands encoded by two genes12. Chromosome mapping using recombinant inbred strains of mice and classic backcrosses show that Mls-la in DBA/2 mice is encoded on chromosome 1, that one of the two ligand genes for deletion of Vβ5 T cells maps to chromosome 12 (ref. 12) and that a ligand gene for Vβ11 deletion is linked to the CDS locus on chromosome 6 (ref. 11). Here we present evidence from three sets of backcross mice for concordance between Vβ11 deletion ligand genes on chromosomes 6,12 and 14 and endogenous mouse mammary tumour virus integrant (Mtv) genomes. Our results indicate that the Vβ11 deletion ligands are products of Mtv genomes.

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

    Lawlor, D. A., Zemmour, J., Ennis, P. D. & Parham, P. A. Rev. Immun. 8, 23–63 (1989).

  2. 2

    White, J. et al. Cell 56, 27–35 (1989).

  3. 3

    Kappler, J. W., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).

  4. 4

    Marrack, P. & Kappler, J. Nature 332, 840–843 (1988).

  5. 5

    Kappler, J. W., Staerz, U., White, J. Nature 332, 35–40 (1988).

  6. 6

    MacDonald, H. R. et al. Nature 332, 40–45 (1988).

  7. 7

    Okada, C. Y., Holzmann, B., Guidos, C., Palmer, E. & Weissman, I. L. J. Immun. 144, 3473–3477 (1990).

  8. 8

    Happ, M. P., Woodland, D. C. & Palmer, E. Proc. natn. Acad. Sci. U.S.A. 86, 6293–6296 (1989).

  9. 9

    Abe, R., Foo-Phllips, M. & Hodes, R. J. J. exp. Med. 170, 1059–1073 (1989).

  10. 10

    Pullen, A. M., Marrack, P. & Kappler, J. W. Nature 335, 796–801 (1988).

  11. 11

    Tomonari, K. & Fairchild, S. Immunogenetics (in the press).

  12. 12

    Woodland, D., Happ, M. P., Bill, J. & Palmer, E. Science 247, 964–967 (1990).

  13. 13

    Tomonari, K. & Lovering, E. Immunogenetics 28, 445–451 (1988).

  14. 14

    Bill, J., Kanagawa, O., Woodland, D. L. & Palmer, E. J. exp. Med. 169, 1405–1419 (1989).

  15. 15

    Gibson, D. M., Maclean, S. J. & Cherry, M. Immunogenetics 18, 111–116 (1983).

  16. 16

    Davidsson, M. T. & Roderick, T. H. in Genetic Variants and Strains of the Laboratory Mouse 2nd edn (eds Lyon, M. F. & Searle, A. G.) 416–427 (Oxford University Press, Oxford, 1989).

  17. 17

    Love, J. M., Knight, A. M., McAleer, M. A. & Todd, J. A. Nucleic Acids Res. 18, 4123–4130 (1990).

  18. 18

    Peters, G. J. Virol. 59, 535–544 (1986).

  19. 19

    Tomonari, K. Immunol. Rev. 116, 139–157 (1990).

  20. 20

    Vacchio, M. S., Ryan, J. J. & Hodes, R. J. J. exp. Med. 172, 807–813 (1990).

  21. 21

    Tomonari, K. Immunogenetics 32, 60–62 (1990).

  22. 22

    Marrack, P. & Kappler, J. Science 248, 705–711 (1990).

  23. 23

    Fraser, J. D. Nature 339, 221–224 (1989).

  24. 24

    Mollick, J. A., Coote, R. G. & Rich, R. R. Science 244, 817–821 (1989).

  25. 25

    Janeway, C. A. Jr Immunol. Rev. 107, 61–88 (1989).

  26. 26

    Henrard, D. & Ross, R. R. J. Virol. 62, 3046–3049 (1988).

  27. 27

    King, L. B., Lund, F. E., White, D. A., Sharma, S. & Corley, R. B. J. Immun. 144, 3218–3227 (1989).

  28. 28

    Heber-Katz, E. & Acha-Orbea, H. Immun. Today 10, 164–169 (1989).

  29. 29

    Maniatis, T., Fritsch, E. F. & Sambrook, J. in Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

  30. 30

    Gebhard, W. & Zachau, H. G. J. molec. Biol. 170, 567–573 (1983).

  31. 31

    Knight, A. M. & Dyson, P. J. Molec. cell. Probes 4, 497–504 (1990).

  32. 32

    Yang, J-N., Boyd, R. T., Gottlieb, P. D. & Dudley, J. P. Immunogenetics 25, 222–227 (1987).

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.