T-CELL REPERTOIRE SELECTION BY MOUSE MAMMARY-TUMOR VIRUSES

Mouse mammary tumour viruses (Mtv) are B-type retroviruses. These can be exogenous, transmitted via maternal milk, or endogenous, as proviral integrations into the mouse genome, transmitted vertically in a Mendelian fashion. A number of different sites of integration of endogenous Mtvs have been reported in various inbred mouse strains. An open reading frame (ORF), within the long terminal repeat (LTR) of Mtv, encodes a type 2 integral membrane glycoprotein. The ORF products are expressed in association with MHC class II molecules at the cell surface and have an affinity for certain T cell receptor (TCR) Vbeta chains such that CD4+8+ TCR+ double positive thymocytes expressing these Vbeta chains undergo programmed cell death in mice carrying the appropriate endogenous or exogenous Mtvs. This constitutes a measurable part of negative repertoire selection of the T cell repertoire. Some positive selection of the T cell repertoire also appears to be TCR Vbeta-specific, although the involvement of polymorphic ligands other than MHC molecules is not apparent. This minireview summarizes the published work on the TCR Vbeta specificity and chromosomal localization of the various mouse mammary tumour proviral integrations leading to negative selection, and discusses the nature of TCR Vbeta-specific positive selection.