High-dimensional mass cytometry provides unparalleled insight into the cellular composition of the immune system. Here, we describe a mass-cytometry-based protocol to examine memory CD4+ Tcell and memory B cell (MBC) responses in human peripheral blood. This approach allows for the identification of >50 distinct memory CD4+ Tcell and MBC populations from a single clinical sample. This highly reproducible protocol has been successfully applied to multiple infectious disease settings to identify correlates of susceptibility or protection from infection. For complete details on the use and execution of this protocol, please refer to Ioannidis etal. (2021).

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