T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool.
SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) nucleates a signaling complex critical for T-cell receptor (TCR) signal propagation. Mutations in the tyrosines of SLP-76 result in graded defects in TCR-induced signals depending on the tyrosine(s) affected. Here we use 2 strains of genomic knock-in mice expressing tyrosine to phenylalanine mutations to examine the role of TCR signals in the differentiation of effector and memory CD8(+) T cells in response to infection in vivo. Our data support a model in which altered TCR signals can determine the rate of memory versus effector cell differentiation independent of initial T-cell expansion. Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production.
Smith-Garvin
Jennifer E
JE
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
Burns
Jeremy C
JC
Gohil
Mercy
M
Zou
Tao
T
Kim
Jiyeon S
JS
Maltzman
Jonathan S
JS
Wherry
E John
EJ
Koretzky
Gary A
GA
Jordan
Martha S
MS
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine