T cell tolerance to Mls^a encoded antigens in T cell receptor Vβ8.1 chain transgenic mice

Abstract

To study T cell tolerance, transgenic mice were generated that expressed the Mlsa-reactive T cell receptor (TCR) β chain Vβ8.1 (cDNA) under the control of the H-2Kb promoter/immunoglobulin heavy chain enhancer on ~ 90% of peripheral T cells. In transgenic mice bearing Mlsa, thymocytes expressing the TCR at a high density were deleted and the percentage of Thy 1.2+ lymph node cells was reduced. The CD4/CD8 ratio of mature T cells was reversed in Mlsa and Mlsb transgenic mice independent of the H-2. RNA analysis and immunofluorescence with TCR Vβ-specific antibodies revealed that expression of endogenous TCR β genes was suppressed. Both Mlsa and Mlsb TCR β chain transgenic mice mounted a T-cell-dependent IgG response against viral antigens, whereas the capacity to generate alloreactive and virus-specific cytotoxic T cells was impaired in TCR β chain transgenic Mlsa, but not in transgenic Mlsb mice.