Light Chain Isotype and Antibody-Specificity Impact on Virus Neutralization

TL;DR

This study shows that the type of light chain in antibodies can affect their virus-neutralizing ability and immune complex formation.

Contribution

The study reveals that light chain isotype and antibody specificity influence antibody function and neutralization activity.

Findings

κ-Abs showed slightly higher thermodynamic stability than λ-Abs.

H4 IgG1κ had increased neutralization and immune complex activity compared to H4 IgG1λ.

Antibody features depend on light chain isotype and antigen specificity.

Abstract

Therapeutic antibodies with lambda light chains (λ-Abs) are underrepresented compared to kappa light chains (κ-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as κ and λ variants. mAbs expressed in glycoengineered Nicotiana benthamiana did not show differences in expression levels, glycosylation, and antigen binding, while κ-Abs exhibited slightly increased thermodynamic stability over λ-Abs. SARS-CoV-2 neutralization and IgG-FcγR immune complex studies revealed increased activities of H4 IgG1κ compared to H4 IgG1λ, with no differences observed between P5C3 variants. Our results indicate that constant light chain variability and Ab specificity contribute to Ab features, a fact that should be considered in engineering therapeutics.

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