Fig. 1: HLA-A2-restricted CD8+ T cells predominantly target conserved spike epitopes.

a Mutation analysis of the ancestral spike amino acid sequence to several variants (top). Lineage (left) and percent sequence conservation from the ancestral strain (right) are depicted. Pile-up histogram of epitopes analyzed in this work and their relative positions are shown. Specific mutations analyzed in this work are shown at the bottom. b Overview of TetTCR-SeqHD workflow and experimental design. c Overview of TCR fingerprinting workflow. d Representative gating for sorting antigen-specific T cells before and after vaccination (left). Summary of pre- (n = 12) and post-vaccine (n = 22) spike tetramer-positive T cell frequencies by flow cytometry (right). Each point represents a unique donor. Mean and standard error of the mean summarizing each group are depicted by the middle line and whiskers, respectively. Pre and Post groups were compared by Student’s t-test (two-sided). **P < 0.01. e Mean TCR frequency (determined by Eq. (3)) of CD8+ T cells targeting spike epitopes before and after vaccination from each donor (CONSERVED, Pre n = 10, Post n = 19; WT, Pre n = 7, Post n = 16; VARIANT, Pre n = 8, Post n = 18; Cross-Reactive, Pre n = 4, Post=4; hCOV, Pre n = 7, Post n = 15). Mean and standard error of the mean summarizing each group are depicted by the middle line and whiskers, respectively. b, c were created in BioRender. Malone, M. (2025) https://BioRender.com/ k17aooq.