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

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 thymus^1–6. 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 deletion^7–11. 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 competence^1–4,12,13. 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–2^s mouse strain is selectively abrogated by blocking class I–K^s molecules but is unaffected by blocking class I-D^s 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.