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CD8/CD4 lineage commitment occurs by an instructional/default process followed by positive selection
Author(s) -
Benveniste Patricia,
Knowles Gisele,
Cohen Amos
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830260229
Subject(s) - biology , cd8 , t cell receptor , microbiology and biotechnology , major histocompatibility complex , cd3 , mhc class i , thymocyte , cytotoxic t cell , antigen , immunology , t cell , in vitro , genetics , immune system
Abstract In the present study, we investigated the developmental potential of purified populations of transitional CD4 in CD8 hi and CD4 hi CD8 in thymocytes that were further defined according to their differentiation stage by their levels of T cell receptor (TCR) expression into TCR lo , TCR in and TCR hi subpopulations. The differentiation potential of each of these subsets was tested in vitro in a single‐cell suspension culture assay that showed that CD4 in CD8 hi TCR hi are precursors of CD8 single‐positive cells, whereas CD4 hi CD8 in TCR in/hi are precursors of both CD4 and CD8 single‐positive thymocytes. The analysis of transitional subsets in mutant mice for either β2‐microglobulin or major histocompatibility complex (MHC) class II further revealed that lineage commitment to the CD8 lineage requires a TCR‐MHC class I engagement, presumably at the immature double‐positive stage of thymic development, while CD4 commitment does not require an MHC class II‐mediated signal, but rather occurs by default. Using the addition of MHC class I‐ or class II‐expressing cells or the addition of total thymocytes to purified sorted transitional precursors for the duration of the cultures in vitro , we identified an additional stage of differentiation for both CD4 and CD8 lineages that requires a positive selection signal. Examination of protein tyrosine phosphorylation of transitional precursors revealed that CD4 in CD8 hi transitional cells contain a high level of a 70‐kDa phosphorylated protein consistent with a role for ZAP70 in the signal transduction during the positive selection of CD8 + cells.