Fig. 4

Challenges of characterization and sequencing of polyclonal antibodies by MS. Variable heavy (VH) and light (VL) chains of human immunoglobulins include semi-variable framework regions (FR1-4) and hypervariable CDRs, with CDR-H3 being the most diverse domain. Sequence logos present the experimental diversity of the matched heavy and light variable chains of 199 B-cell clones secreting anti-spike SARS-CoV-2 antibodies, based on reanalysis of data for a single convalescent donor [158]. The framework regions are encoded by the germline V- and J-genes, are minimally affected by affinity maturation, and include some well-conserved sequences (YYCAR, etc.) suitable as sequence tags for the hybrid de novo sequencing approaches