Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.
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.
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Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell, alpha-beta
- Mice, Transgenic
- Mice
- Major Histocompatibility Complex
- Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
- Immunoprecipitation
- Immunology
- Fluorescent Antibody Technique
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell, alpha-beta
- Mice, Transgenic
- Mice
- Major Histocompatibility Complex
- Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
- Immunoprecipitation
- Immunology
- Fluorescent Antibody Technique