The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling
Significant number of STC per cell only forms under limited conditions. (a) Schematic representation of a tetravalent aggregate () binding to BCRs to form , where denotes the number of BCRs bound to . Black arrow points out the binding of to a BCR. Each binding step is governed by its binding () and dissociation () rates. (b) Simulated levels of STC formed per cell are plotted against percentage of antigen-specific B cells under low (L, 0.1 pM), medium (M, 12 pM), and high (H, 1500 pM) levels of total , for binding affinity pM−1 (left panel), 10−5 pM−1 (middle panel), and 10−3 pM−1 (right panel). Inset in the right panel is the zoomed-in version of the plot. STC per B cell is defined as the number of aggregates that cross-link a minimum number () of BCRs. Here and valency . The horizontal dashed line denotes one STC.
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