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. Author manuscript; available in PMC: 2023 Apr 11.
Published in final edited form as: Immunity. 2022 Jan 5;55(2):341–354.e7. doi: 10.1016/j.immuni.2021.12.003

Figure 6. VH1-69 CDRH1 somatic mutations are critical for broad HCV neutralization.

Figure 6.

(A) Left panel: alignment of amino acid sequences of 12 HCV antibodies to VH1-69*01 (K73 is encoded by the VH1-69*06 germline allele and therefore is not necessarily a somatic mutation). Right panel: effect of partial germline-reversion on HCVcc neutralization at an antibody concentration of 50 μg/mL. Medians of triplicate measurements. Th, threshold.

(B) Effect of single VH1-69 amino acid germline-reversions on HCVcc neutralization. The reverted mutations are also highlighted in (A) in red. Means ± SD of triplicate measurements.

(C) HCVcc average neutralization (6-virus panel) by antibodies with VH gene segments reverted to germline, except for the CDRH1.

Medians of triplicate measurements. Representative of 3 (A) or 2 (B and C) independent experiments. Not significant (n.s.), *p ≤ 0.05, **p ≤ 0.01; Wilcoxon matched-pairs signed rank test with Bonferroni correction. Average neutralization values across all 6 tested HCVcc strains for each mutated antibody were compared pairwise with average neutralization values of corresponding original antibodies (A) or among each other (C). GL, germline. See also Figure S4.