Data Sheet 2_Antibodies and cryptographic hash functions: quantifying the specificity paradox.pdf

The specificity of the immune response is critical to its biological function, yet the generality of immune recognition implies that antibody binding is multispecific or degenerate. The current work explores and quantifies this paradox through a systems analysis approach that incorporates set theoretic ideas and an application of structural and statistical modeling to prior experimental immunological and biochemical data. Order-of-magnitude estimates are computed for the average degeneracies and specificities of antibodies and epitopes using a chemico-spatial model for epitope diversity and a binary model for antibody-antigen binding. The results illustrate and quantify how the humoral immune system achieves both high specificity and high degeneracy simultaneously by effectively decoupling the two properties, similarly to programs in cryptography called secure hash algorithms (SHAs), which display the same paradoxical features. In addition, an antibody-epitope interaction probability model is used to help show how newly formed antibodies may avoid cross-reactivity with self-antigens despite their high degree of multispecificity and how the requirement of polyclonal binding likely improves the overall specificity of the immune response. Because they describe the relationships between various statistical parameters in humoral immunity, the models developed here may also have predictive utility.

免疫应答的特异性对于其生物学功能至关重要，然而免疫识别的普遍性却提示抗体结合具有多特异性或简并性。本研究采用融合集合论思想的系统分析方法，将结构建模与统计建模应用于既往免疫学及生物化学实验数据，以此探究并量化这一悖论。本研究借助表征表位（epitope）多样性的化学空间模型，以及抗体-抗原结合的二元模型，计算得到抗体与表位的平均简并度及特异性的数量级估算值。研究结果阐明并量化了体液免疫系统如何通过有效解耦特异性与简并性这两种特性，同时实现高特异性与高简并性——这一机制与密码学领域的安全散列算法（SHAs）类似，后者同样具备这类悖论性特征。此外，本研究通过抗体-表位相互作用概率模型，阐释了新生抗体尽管具备高度多特异性，却如何避免与自身抗原发生交叉反应，以及多克隆结合的需求何以能够提升免疫应答的整体特异性。由于本研究构建的模型描述了体液免疫中各类统计参数间的关联，因此这些模型同样具备预测应用价值。