Abstract
Following infection, naïve CD8+ T cells bearing pathogen-specific T cell receptors (TCRs) differentiate into a mixed population of short-lived effector and long-lived memory T cells to mediate an adaptive immune response. How the TCR regulates memory T cell development has remained elusive. Using a mutant TCR transgenic model, we found that point mutations in the TCR beta transmembrane domain (betaTMD) impair the development and function of CD8+ memory T cells without affecting primary effector T cell responses. Mutant T cells are deficient in polarizing the TCR and in organizing the nuclear factor kappaB signal at the immunological synapse. Thus, effector and memory states of CD8+ T cells are separable fates, determined by differential TCR signaling.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adoptive Transfer
-
Animals
-
Antigen-Presenting Cells / immunology
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation
-
Genes, T-Cell Receptor beta
-
Immunization
-
Immunologic Memory*
-
Immunological Synapses / immunology
-
Listeria monocytogenes
-
Listeriosis / immunology
-
Lymphocyte Count
-
Mice
-
Mice, Transgenic
-
NF-kappa B / metabolism*
-
Point Mutation
-
Protein Structure, Tertiary
-
Receptors, Antigen, T-Cell, alpha-beta / chemistry
-
Receptors, Antigen, T-Cell, alpha-beta / genetics
-
Receptors, Antigen, T-Cell, alpha-beta / immunology
-
Receptors, Antigen, T-Cell, alpha-beta / metabolism*
-
Signal Transduction*
-
T-Lymphocyte Subsets / cytology
-
T-Lymphocyte Subsets / immunology*
Substances
-
NF-kappa B
-
Receptors, Antigen, T-Cell, alpha-beta