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Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. klaky@niaid.nih.gov
MHC specificity in positive selection is a major determinant in the CD4/CD8 T cell lineage decision. Previous studies support the view that quantitative differences in T cell receptor (TCR) signaling in immature CD4+CD8+ double positive thymocytes leads to an instructive bias in CD4/CD8 T cell lineage commitment that must be re-inforced in subsequent selection steps to ensure that MHC-restricted antigen recognition is linked to appropriate effector functions in mature T cells. Recent work has further defined the TCR signaling pathways involved in this process, but a major effort has been made to identify transcription factors and other regulators of CD4 and CD8 T cell lineage commitment. Methods and screens for detecting changes in gene expression, associated with TCR signaling in positive selection and lineage determination, are starting to provide a better understanding of these complex developmental processes.
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