The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire

Mark T. Scherer, Leszek Ignatowicz, Ann Pullen, John Kappler, Philippa Marrack

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3′ long terminal repeats of endogenous mammary tumor viruses (Mtv’s). A line of Mtv-negative mice and several lines of mice containing single Mtv’s were created by inbreeding the F2 progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2k mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the Vβ repertoire, there are no superantigens, other than those encoded by Mtv’s, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv-negafive mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection, vSAG3 was found to delete Vβ5 T cells, while vSAG8 deleted Vβ7 T cells, and vSAG9 deleted Vβ13 T cells in addition to their previously reported specificities, vSAG17 deletes a small proportion ofCD4+ T cells bearing Vβ11 and -12. vSAG14 and -30 have httle effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular Vβ may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant Vβs. We found evidence that vSAG11 may positively select T cells bearing Vβ8.2. Our data, which analyzed the effects of seven endogenous Mtv’s, showed little evidence of positive selection by any other vSAGs on T cells bearing any Vβ tested, despite published reports to the contrary.

Original languageEnglish (US)
Pages (from-to)1493-1504
Number of pages12
JournalJournal of Experimental Medicine
Volume182
Issue number5
DOIs
StatePublished - Nov 1 1995

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Mouse mammary tumor virus
Superantigens
Oncogenic Viruses
Breast Neoplasms
T-Lymphocytes
Thymocytes
Genes
Inbreeding
Terminal Repeat Sequences
Major Histocompatibility Complex

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire. / Scherer, Mark T.; Ignatowicz, Leszek; Pullen, Ann; Kappler, John; Marrack, Philippa.

In: Journal of Experimental Medicine, Vol. 182, No. 5, 01.11.1995, p. 1493-1504.

Research output: Contribution to journalArticle

Scherer, Mark T. ; Ignatowicz, Leszek ; Pullen, Ann ; Kappler, John ; Marrack, Philippa. / The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire. In: Journal of Experimental Medicine. 1995 ; Vol. 182, No. 5. pp. 1493-1504.
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