Positive selection of CD4-CD8+ T cells in the thymus of normal mice

Publisher Website
Google Scholar
Abstract
THE diversification of the repertoire of T-cell antigen receptor (TCR) specificities is influenced by at least two selection processes which occur in the thymus1–6. One of these, termed "negative selection", is required to install a state of tolerance to self-antigens in the T-cell repertoire and is often achieved by clonal deletion7–11. The second type of selection operating in the thymus results in preferential differentiation of T cells that have restriction specificity for thymic major histocompatibility complex glyco-proteins, but the mechanisms leading to this selective process are not yet clear. One model used to describe this "positive selection" proposes that only those T cells with sufficient avidity for the MHC glycoproteins expressed in the thymus are allowed to acquire functional competence1–4,12,13. Here we directly investigate the generation of TCR specificities by following the fate of developing Vβ17+ CD4-CD8+ T cells under conditions where one of the main class I-MHC molecules, either H–2K or H–2D, was specifically blocked by in vitro monoclonal antibody treatment14. The results show that development of Vβ17+ CD4-CD8+ T cells in the SJL H–2s mouse strain is selectively abrogated by blocking class I–Ks molecules but is unaffected by blocking class I-Ds molecules. These data directly demonstrate that generation of CD4-CD8+ T cells expressing a particular TCR Vβ segment can be correlated with the expression of a particular class I-MHC molecule, thereby providing evidence for positive selection.