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. (Blood. 2010; 116(25): 5548-5559)