Self-reactive T cells can escape clonal deletion in T-cell receptor Vβ8.1 transgenic mice

Abstract

To study the mechanisms of tolerance in detail, we have constructed transgenic mice expressing a Vβ8.1-Dβ2-Jβ2.3-C β2 T-cell receptor (TCR) gene. Since expression of Vβ8.1 is known to correlate with reactivity of CD4+CD8- T cells to minor lymphocyte-stimulating locus 1a (Mls-1a), we expected to induce tolerance in most CD4+CD8- T cells in Vβ8.1 transgenic mice of the Mls-1a allele. In one line of Mls-1b Vβ8.1 transgenic mice, the Vβ8.1 TCR was expressed on >98% of mature T cells and their response to Mis-1a was highly enriched. In Mls-1a Vβ8.1 transgenic mice, CD4+CD8- T cells in these mice were severely reduced among both peripheral T cells and thymocytes. However, the deletion of these cells was not complete, and most of the residual CD4+CD8- mature T cells still expressed normal densities of Vβ8.1 TCR. The residual CD4+CD8- T cells did not respond to Mls-1a but were still able to proliferate in response to other stimuli via the TCR. Interestingly, CD4+CD8- Vβ8.1+ T-cell clones isolated from Mls-1a Vβ8.1 transgenic mice could respond to Mls-1a. We suggest that these types of T cells escape clonal deletion in the thymus.