Regulation of lineage commitment distinct from positive selection

Science. 1999 Nov 5;286(5442):1149-53. doi: 10.1126/science.286.5442.1149.

Abstract

Developing alphabeta T cells diverge into the CD4 and CD8 lineages as they mature in the thymus. It is unclear whether lineage commitment is mechanistically distinct from the process that selects for the survival of T cells with useful T cell receptor (TCR) specificities (positive selection). In HD mice, which lack mature CD4+ T cells, major histocompatibility complex (MHC) class II-restricted T cells are redirected to the CD8 lineage independent of MHC class I expression. However, neither TCR-mediated signaling nor positive selection is impaired. Thus, the HD mutation provides genetic evidence that lineage commitment may be mechanistically distinct from positive selection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Lineage*
  • Crosses, Genetic
  • Female
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Phenotype
  • Phosphorylation
  • Radiation Chimera
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell, alpha-beta