IL-18 and perforin deficiency drive oligoclonal CD8 T-cell hyperexpansion unaffected by broad-spectrum antibiotic treatment. (A) A bubble plot represents the proportion of mapped TCRs attributable to individual clonotypes within Prf1^⁻/⁻, Il18tg, DS^HET, and DS^KO mice. (B) Sums of the proportion of mapped TCRs attributable to clonotypes that individually occupy a large (0.1% to 1%) or hyperexpanded (1% to 100%) proportion of all mapped TCRs. (C) Representative plot showing that the top 50 hyperexpanded clonotypes in a single DS^KO mouse account for ∼50% of all mapped TCRs in that mouse, but the same clonotypes account for a negligible proportion of all mapped TCRs in all other sequenced mice. (D) Splenomegaly, anemia, and thrombocytopenia in DS^KO mice after >30 days of antibiotic treatment with metronidazole, neomycin, ampicillin, and vancomycin. The dotted line represents the average platelet count for WT mice. (E) CD8 T-cell activation and ex vivo stimulated IFN-γ production in DS^KO mice after treatment. All graphs are combined from 2 experiments; each point represents an individual mouse.