{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen HT"],"funding":["NIA NIH HHS","NIAID NIH HHS","Boehringer Ingelheim","National Institutes of Health","NIGMS NIH HHS","National Science Foundation"],"pagination":["114801"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11564698"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(10)"],"pubmed_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"],"journal":["Cell reports"],"pubmed_title":["Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions."],"pmcid":["PMC11564698"],"funding_grant_id":["R01 AG080016","R35 GM136300","DGE 1256260","RF1AG059723","R21AI171844","R21 AI171844","RF1 AG059723","R01AG080016","R35GM136300"],"pubmed_authors":["Xie Y","Chen HT","Huang J","Tessier PM","Desai AA","Kumar S","Sawant M","Zhang Y","Makowski E","Licari G","Rajagopal N","Marlow MS","Smith MD"],"additional_accession":[]},"is_claimable":false,"name":"Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.","description":"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","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-18T17:00:17.17Z","creation":"2025-04-07T04:31:18.727Z"},"accession":"S-EPMC11564698","cross_references":{"pubmed":["39392756"],"doi":["10.1016/j.celrep.2024.114801"]}}