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Sun, L; Palt, R; Schütz, G; Föderl-Hoebenreich, E; Brod, L; Hermle, A; Lux, A; Steinkellner, H; Kallolimath, S.
Light Chain Isotype and Antibody-Specificity Impact on Virus Neutralization
ANTIBODIES. 2025; 14(2): 50
Doi: 10.3390/antib14020050
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- Co-Autor*innen der Med Uni Graz
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Föderl-Höbenreich Esther
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- Abstract:
- Therapeutic antibodies with lambda light chains (lambda-Abs) are underrepresented compared to kappa light chains (kappa-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as kappa and lambda variants. mAbs expressed in glycoengineered Nicotiana benthamiana did not show differences in expression levels, glycosylation, and antigen binding, while kappa-Abs exhibited slightly increased thermodynamic stability over lambda-Abs. SARS-CoV-2 neutralization and IgG-Fc gamma R immune complex studies revealed increased activities of H4 IgG1 kappa compared to H4 IgG1 lambda, 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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kappa-lambda light chain
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monoclonal antibodies
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SARS-CoV-2
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Fc gamma-receptor binding
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virus neutralization
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stability