Different antibody lineages can undergo convergent evolution during affinity maturation

Summary

Different antibody and nanobody lineages, including those from different germlines, can undergo convergent evolution during affinity maturation (1,2). This includes binding to the same epitope in the same place (3,4). For cases with the same germline, this can happen both within the same immune repertoire and across different organisms exposed to the same antigen. Convergent evolution across different VH germlines can also arise in the same individual (5).

Details

Ogega et al. found that three antibody lineages, taken from the same person, independently evolved the same three somatic (non-germline) mutations in CDRH1 and CDRH2 (5).

De Genst et al. found that distinct nanobodies shared the same D gene and non-germline mutations in CDR2 (4).

Figures

Ref (2)

Ref (5)

Ref (4)

See also

• GRAB motifs

1.

Robinson WH. Sequencing the functional antibody repertoire—diagnostic and therapeutic discovery. Nature Reviews Rheumatology. 2014;11(3):171–82. Available from: https://doi.org/10.1038/nrrheum.2014.220

2.

Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science. 2011;333(6049):1593–602. Available from: https://doi.org/10.1126/science.1207532

3.

Malby RL, Tulip WR, Harley VR, McKimm-Breschkin JL, Laver WG, Webster RG, et al. The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. Structure. 1994;2(8):733–46. Available from: https://doi.org/10.1016/s0969-2126(00)00074-5

4.

De Genst E, Silence K, Ghahroudi MA, Decanniere K, Loris R, Kinne J, et al. Strong in Vivo Maturation Compensates for Structurally Restricted H3 Loops in Antibody Repertoires. Journal of Biological Chemistry. 2005;280(14):14114–21. Available from: https://doi.org/10.1074/jbc.m413011200

5.

Ogega CO, Skinner NE, Schoenle MV, Wilcox XE, Frumento N, Wright DA, et al. Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance. Immunity. 2024;57(4):890-903.e6. Available from: https://doi.org/10.1016/j.immuni.2024.03.001