Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC

Immunity. 2007 Nov;27(5):735-50. doi: 10.1016/j.immuni.2007.10.007.


The thymus generates major histocompatibility complex (MHC)-restricted alphabetaT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alphabetaTCR repertoire during thymic selection by CD4 and CD8 coreceptors that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alphabeta thymocytes would be signaled by non-MHC ligands to differentiate into alphabetaT cells lacking MHC specificity. We now report that MHC-independent alphabetaT cells were indeed generated in mice deficient in both coreceptors as well as MHC ("quad-deficient" mice) and that such mice contained a diverse alphabetaT cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alphabetaTCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Blotting, Northern
  • CD4 Antigens / immunology*
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology*
  • CD8 Antigens / metabolism
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Immunoprecipitation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology


  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell, alpha-beta
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)