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Two separable T cell receptor signals reconstitute positive selection of CD4 lineage T cells in vivo
Author(s) -
Schmitt Steffen,
Müller KlausPeter,
Kyewski Bruno A.
Publication year - 1997
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.1830270904
Subject(s) - biology , t cell receptor , cd8 , major histocompatibility complex , microbiology and biotechnology , lineage (genetic) , mhc class i , t cell , cellular differentiation , cytotoxic t cell , mhc class ii , immunology , antigen , genetics , immune system , in vitro , gene
Abstract Positive selection is an obligatory step during intrathymic T cell differentiation. It is associated with rescue of short‐lived, self major histocompatibility complex (MHC)‐restricted thymocytes from programmed cell death, CD4/CD8 T cell lineage commitment, and induction of lineage‐specific differentiation programs. T cell receptor (TCR) signaling during positive selection can be closely mimicked by targeting TCR on immature thymocytes to cortical epithelial cells in situ via hybrid antibodies. We show that selection of CD4 T cell lineage cells in mice deficient for MHC class I and MHC class II expression can be reconstituted in vivo by two separable T cell receptor signaling steps, whereas a single TCR signal leads only to induction of short‐lived CD4 + CD8 la intermediates. These intermediates remain susceptible to a second TCR signal for 12‐48 h providing an estimate for the duration of positive selection in situ. While both TCR signals induce differentiation steps, only the second one confers long‐term survival on immature thymocytes. In further support of the two‐step model of positive selection we provide evidence that CD4 T cell lineage cells rescued by a single hybrid antibody pulse in MHC class II‐deficient mice are pre‐selected by MHC class 1.