Simultaneous Coexpression of Memory-related and Effector-related Genes by Individual Human CD8 T Cells Depends on Antigen Specificity and Differentiation

• DOI: 10.1097/cji.0b013e31826183a7
• Publication Date: 2012-12-17T19:56:45Z
• Authors: Bhawna Gupta; Emanuela M. Iancu; Philippe O. Gannon; Sébastien Wieckowski; Lukas Baitsch; Daniel E. Speiser; Nathalie Rufer
• Keywords: Memory T cell; Homing (biology); Streptamer; CXCR3

Phenotypic and functional cell properties are usually analyzed at the level of defined populations but not single cells. Yet, large differences between individual cells may have important consequences. It is likely that T-cell–mediated immunity depends on polyfunctionality T cells, rather than sum functions responding T-cell subpopulations. We performed highly sensitive single-cell gene expression profiling, allowing direct ex vivo characterization virus-specific tumor-specific from healthy donors melanoma patients. previously shown vaccination with natural tumor peptide Melan-AMART-1-induced superior effector as compared analog optimized for enhanced HLA-A*0201 binding. Here we found induced tumor-reactive CD8+ frequent coexpression both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3, CCR5) effector-related (IFNG, KLRD1, PRF1, GZMB), comparable protective Epstein-Barr cytomegalovirus-specific In contrast, effector-associated were less frequently coexpressed after peptide. Remarkably, these findings reveal a unknown diversity among vaccine-specific simultaneous multiple memory/homing-related by same cell. Such broad signatures within antigen-specific be critical mounting efficient responses to pathogens or tumors. summary, high-resolution molecular provides key insights into processes shaping