High-dimensional analysis of human CD8(+) T cell phenotype, function, and antigen specificity.

Antigen-specific T cells are critical initiators and orchestrators of the adaptive immune response. Categorizing antigen-specific T cell subsets is not a simple task given the diversity of these cells and the large number of parameters that can be considered. Here, we focus on human CD8(+) T cells and discuss the utility of high-dimensional mass cytometric analysis techniques for the concurrent identification and characterization of antigen-specific T cells involved in immunological homeostasis and disease. We first provide an overview of previously identified T cell subsets. We then discuss the segregation of antigen-specific T cells based on protein expression through surface and/or intracellular staining, on functional capacity through measurement expression of cytokines or other inducible markers, and on the antigen-specificity of the cell assessed using peptide-major histocompatibility complex multimers. High-dimensional mass cytometry enables a deeper and more integrated view of all three aspects of antigen-specific T cell diversity than do traditional techniques. Use of mass cytometry for precise measurement of the status of antigen-specific immune responses should result in better prediction of vaccine efficacy and disease outcomes.