T-CELL DEVELOPMENT AND REPERTOIRE OF MICE EXPRESSING A SINGLE T-CELL RECEPTOR-ALPHA CHAIN

We examined T cell development and T cell repertoire in transgenic mice expressing a single T cell receptor (TCR) alpha chain derived from the H-2D(b)-lymphocytic choriomeningitis virus (LCMV)-specific cytolytic T lymphocyte (CTL) clone P14. To generate these alpha P14 mice, mice transgenic for the P14 TCR ct chain were backcrossed to TCR alpha-deficient mice, Thymi from alpha P14 mice exhibited a marked decrease of mature CD4(+)8(-) and CD8(+)4(-) single-positive thymocytes comparable to thymi from TCR alpha-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 alpha 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 V beta-specific antibodies showed a diverse endogenous TCR V beta 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 alpha chain.