Different T cell receptor signals determine CD8+ memory versus effector development.
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.
Teixeiro
Emma
E
Experimental Transplantation Immunology, Department of Biomedicine, University Hospital-Basel, Hebelstrasse 20, 4031-Basel, Switzerland. teixeiropernase@missouri.edu
Daniels
Mark A
MA
Hamilton
Sara E
SE
Schrum
Adam G
AG
Bragado
Rafael
R
Jameson
Stephen C
SC
Palmer
Ed
E
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D019674:Genes, T-Cell Receptor beta; D007114:Immunization; D007156:Immunologic Memory; D054992:Immunological Synapses / Q000276:immunology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D016328:NF-kappa B; D016693:Receptors, Antigen, T-Cell, alpha-beta