Simultaneous analysis of antigen‐specific B and T cells after SARS‐CoV‐2 infection and vaccination

Conventional methods for quantifying and phenotyping antigen‐specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen‐specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen‐specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B and T cell tandem lymphocyte evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS‐CoV‐2 Spike reactive T and B cells using an activation induced marker (AIM) T cell assay and dual‐color B cell antigen probes. Using this assay, we demonstrate that antigen‐specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS‐CoV‐2 infection.