T cell development and repertoire of mice expressing a single T cell receptor α chain |
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Authors: | Daniel Brndle Karin Brduscha-Riem Adrian C Hayday Michael J Owen Hans Hengartner Hanspeter Pircher |
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Institution: | Daniel Brändle,Karin Brduscha-Riem,Adrian C. Hayday,Michael J. Owen,Hans Hengartner,Hanspeter Pircher |
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Abstract: | We examined T cell development and T cell repertoire in transgenic mice expressing a single T cell receptor (TCR) α chain derived from the H-2Db -lymphocytic choriomeningitis virus (LCMV)-specific cytolytic T lymphocyte (CTL) clone P14. To generate these α P14 mice, mice transgenic for the P14 TCR α chain were backcrossed to TCR α-deficient mice. Thymi from α P14 mice exhibited a marked decrease of mature CD4+8? and CD8+4? single-positive thymocytes comparable to thymi from TCR α-deficient mice. Correspondingly, the number of peripheral T cells was reduced in the CD4 (tenfold) and in the CD8 (twofold) subsets when compared to normal mice. T cells from α P14 mice generated a primary anti-LCMV CTL response when stimulated in vitro with LCMV in contrast to normal mice which require priming in vivo; elimination of LCMV in vivo was, however, not improved. Flow cytometric analysis of T cells with Vβ-specific antibodies showed a diverse endogenous TCR Vβ repertoire. Functional analysis of the T cell repertoire, however, revealed a strongly reduced (30-fold) allogeneic and the absence of a vesicular stomatitis virus-specific CTL response and an impaired ability to provide T cell help for antibody isotype switching. Thus, T cell selection in the thymus was impaired and the T cell repertoire was limited in mice expressing only one type of TCR α chain. |
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Keywords: | TCR α -deficient mice TCR α -transgenic mice Allelic exclusion T cell repertoire Positive selection |
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