Figure 3.
VRC01gHL mAbs acquire bnAb-like VRC01-class mutations after MD39-GT3.1 immunization
(A) Accumulation of HC and LC amino acid mutations in VRC01gHL BGC cells. n is the total number of sequences analyzed. Detailed sampling information is presented in Figure S4.
(B) Day 36 per-residue mutation frequency of HC and LC amino acid residues. Residue positions are numbered linearly.
(C) List of IGHV1-2-region VRC01-class mutations.
(D) Total and VRC01-class amino acid mutations in the IGHV1-2 region. The diagonal red line represents maximum VRC01-class mutations. The staircase shows the background level of random mutations.
(E) Most frequently mutated HC residues on day 36. Shades of blue indicate VRC01-class mutations. Asterisks indicate VRC01 matched mutations. Red shades indicate SHMs not observed in our reference VRC01-class antibodies. Residues are shown in Kabat numbering.
(F) VRC01 HC CDR loop conformations are stabilized via H-CDR1N35-H-CDR3N100a and H-CDR1C32-H-CDR3C98 interactions (purple sticks). VRC01gHL cells from MD39-GT3.1-immunized mice achieve the stabilizing interaction via H-CDR1H32-H-CDR3S98 (blue sticks) or H-CDR1N35-H-CDR3N100a (PDB: 4JPI).
(G) Mutations observed in HC position S54.
(H) Day 36 LC mutations observed in S30. Color coding is as in (D).
(I) Selection of arginine residues in L-CDR1 positions 30 and 31 on day 36 after immunization with the MD39-GT3.1 trimer or eOD-GT5 60-mer.