Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.

ABSTRACT: Although antibody variable regions mediate antigen-specific binding, they can also mediate non-specific interactions with non-cognate antigens, impacting diverse immunological processes and the efficacy, safety, and half-life of antibody therapeutics. To understand the molecular basis of antibody non-specificity, we sorted two dissimilar human naïve antibody libraries against multiple reagents to enrich for variants with different levels of polyreactivity. Sequence analysis of >300,000 paired antibody variable regions revealed that the heavy chain primarily mediates human antibody polyreactivity, and this is due to the high positive charge, high hydrophobicity, and combinations thereof in the corresponding complementarity-determining regions, which can be predicted using a machine learning

SUBMITTER: Chen HT 

PROVIDER: S-EPMC11564698 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature