查看文章

CD8⁺ T cells recognizing antigenic peptides derived from conserved internal viral proteins confer broad protection against distinct influenza viruses. As memory CD8⁺ T cells change throughout the human lifetime and across tissue compartments, we investigated how T cell receptor (TCR) composition and diversity relate to memory CD8⁺ T cells across anatomical sites and immunological phases of human life. We used ex vivo peptide-HLA tetramer magnetic enrichment, single-cell multiplex RT-PCR for both the TCR-alpha (TCRα) and TCR-beta (TCRβ) chains, and new TCRdist and grouping of lymphocyte interactions by paratope hotspots (GLIPH) algorithms to compare TCRs directed against the most prominent human influenza epitope, HLA-A*02:01-M1_58–66 (A2⁺M1₅₈). We dissected memory TCR repertoires directed toward A2⁺M1₅₈ CD8⁺ T cells within human tissues and compared them to human peripheral blood of young and elderly adults. Furthermore, we compared these memory CD8⁺ T cell repertoires to A2⁺M1₅₈ CD8⁺ TCRs during acute influenza disease in patients hospitalized with avian A/H7N9 virus. Our study provides the first ex vivo comparative analysis of paired antigen-specific TCR-α/β clonotypes across different tissues and peripheral blood across different age groups. We show that human A2⁺M1₅₈ CD8⁺ T cells can be readily detected in human lungs, spleens, and lymph nodes, and that tissue A2⁺M1₅₈ TCRαβ repertoires reflect A2⁺M1₅₈ TCRαβ clonotypes derived from peripheral blood in healthy adults and influenza-infected patients. A2⁺M1₅₈ TCRαβ repertoires displayed distinct features only in elderly adults …