CD8+ T lymphocytes in double alpha beta TCR transgenic mice. I. TCR expression and thymus selection in the absence or in the presence of self-antigen.

Abstract

We derived Rag2-deficient mice bearing two rearranged alphabeta TCR transgenes, one specific for the HY male Ag and the second specific for the gp33-41 peptide of lymphocytic choriomeningitis virus, both restricted to the MHC H-2D(b) class I molecule. We found that, in female double transgenic (DTg) mice, most CD8 T cells express only the TCRbeta chain from the aHY transgene. By comparing the mRNA species for both beta-chains, we observed that in T cells from DTg mice the aHY TCRbeta chain transcripts are abundant, whereas the anti-lymphocytic choriomeningitis virus TCRbeta chain transcripts are rare. In contrast to TCRbeta chain expression, most of the T cells from DTg mice express two TCRalpha chains. We examined the thymus selection of the dual-receptor CD8 T cells in the presence of self-Ag. We found that the presence of a second TCRalpha chain allows a significant number of CD8 T cells expressing a self-reactive receptor to escape central deletion and migrate to the peripheral pools of male mice. Differences in TCR and coreceptor expression between female and male MoaHY and DTg mice suggest that peripheral T cell survival requires an optimal level of signaling, which implies a process of "adaptation" of lymphocyte populations to the host environment.