To evaluate T cell reactivity to antigenic challenge, a Reactivity Score (RS) metric was generated from the analysis of cell populations defined by the combined expression of 4 AIMs. These markers and 3 gated areas of interest (Single +, Double +, and “All”) were used to define a total of 16 partially overlapping cell populations ( Supplementary Figure S1A , Supplementary Table S2 ). We selected T cell populations whose response (frequency after stimulus minus background frequency) was significantly higher in healthy controls than HSCT patients and normalized each value by the average frequency of all measurements for that population. When the frequency after stimulation was smaller than the background (frequency after stimulus minus background frequency < 0), the patient was assigned a RS value of ‘zero’. The RS for each patient was then computed by averaging the normalized frequency of the selected populations for each T cell subset (selected T cell populations are shown in Supplementary Figure S2 ). Similarly, the score for differential reactivity (DR) was computed by normalizing the difference in T cell response to Spike-C and Spike-I pool stimulation (Spike-C minus Spike-I). The T cell populations selected for DR calculation are shown in Supplementary Table S2 . Raw frequency data for each population are reported in Supplementary Table S3 .
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