Identification of B cell epitopes enhanced by protein unfolding and aggregation

Publication date: January 2019Source: Molecular Immunology, Volume 105Author(s): Timothy J. Eyes, James I. Austerberry, Rebecca J. Dearman, Linus O. Johannissen, Ian Kimber, Noel Smith, Angela Thistlethwaite, Jeremy P. DerrickAbstractAggregation of therapeutic proteins is a key factor in the generation of unwanted immunogenicity, and can result in reduced serum half-life, neutralization of function and adverse health effects. There is currently little information regarding how aggregates interact with B-cell receptors or cognate antibodies at the protein sequence level, or whether non-native, aggregate-induced epitopes predominate in these interactions. Using an antibody fragment (single chain antibody variable fragment; scFv) that forms aggregates readily at low temperature, anti-scFv IgG...

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