T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous α- and β-genes

Abstract

In B cells the loci encoding immunoglobulin chains usually show allelic exclusion; a given B cell transcribes and translates only one productively rearranged allele of the heavy and light chain loci^1–3. This ensures that each B cell expresses only one antigen receptor. The loci encoding T-cell receptor (TCR) α- and β- genes may behave similarly^4–6. We have previously reported that the expression of a transgenic TCR β-chain prevents functional and nonfunctional V_β rearrangements in the endogenous β-chain loci but not D_βJ_β rearrangements⁷. We have also been unable to detect the expression of the TCR γ-chain locus in thymocytes of these mice (unpublished observations). To study the mechanisms involved in forming a mature T-cell repertoire further, we have constructed mice expressing α- and β-TCR transgenes derived from a cytotoxic T-cell clone that is specific for the male antigen H-Y in the context of H–2D^b MHC molecules. Here we show that in these mice rearrangement of endogenous α-chain loci is also suppressed, although to a lesser extent than rearrangement of β-chain loci. In addition, in male αβ TCR transgenic mice we observed T-cell clones which had deleted both transgenic α- and β-chain genes and expressed endogenous α- and β-chain TCR genes. These cells are presumably derived from rare thymocytes that leave the male thymus because their TCR no longer recognizes self antigen. The vast majority of CD4⁺8⁺ nonmature thymocytes expressing α-and β-transgenes are deleted in the male thymus⁸.