THEORETICAL-STUDIES OF CLONAL SELECTION - MINIMAL ANTIBODY REPERTOIRE SIZE AND RELIABILITY OF SELF-NON-SELF DISCRIMINATION
THEORETICAL-STUDIES OF CLONAL SELECTION - MINIMAL ANTIBODY REPERTOIRE SIZE AND RELIABILITY OF SELF-NON-SELF DISCRIMINATION
复制标题
DOI：
10.1016/0022-5193(79)90275-3
复制
发表时间：
1979-01-01
影响因子：
2
通讯作者：
OSTER, GF
中科院分区：
文献类型：
--
作者：
PERELSON, AS;OSTER, GF
将免疫系统视为设计用于识别外来形状的分子识别装置，估计了在其库中具有NAb单特异性抗体的免疫系统可以识别随机外来抗原的概率。如果抗体是多特异性的而不是单特异性的，则估计识别的改善。从该概率模型中，得出以下结论：克隆选择是可行的，即，利用有限数量的抗体，动物可以有效地识别无限数量的抗原;不同物种之间的抗体分子的特异性不应该有很大的差异;抗体识别的外来分子的区域在程度上必须严格限制;识别外来分子的概率P随着抗体库大小NAb的增加而增加，低于一定值的NAb，免疫系统将非常无效，而超过NAb的某个高值，NAb的进一步增加会减少P的小幅增加。多特异性相当于适度增加在抗体库大小NAb中，这种增加可以显著增加（可能小于10），但这种增加可以显著提高免疫系统识别外源分子的概率。除了识别外来分子外，免疫系统还必须将它们与自身分子区分开来。使用可靠性的数学理论，多位点识别是一种比单位点识别更可靠的区分分子的方法。这可能是在选择弱非共价相互作用作为抗原-抗体键的基础时的重要进化考虑。
Viewing the immune system as a molecular recognition device designed to identify foreign shapes, the probability that an immune system with NAb monospecific antibodies in its repertoire can recognize a random foreign antigen was estimated. The improvement in recognition if antibodies are multispecific rather than monospecific was estimated. From this probabilistic model, the following were concluded: clonal selection is feasible, i.e., with a finite number of antibodies an animal can recognize an effectively infinite number of antigens; there should not be great differences in specificities of antibody molecules among different species; the region of a foreign molecule recognized by an antibody must be severely limited in extent; the probability of recognizing a foreign molecule, P, increases with the antibody repertoire size NAb and below a certain value of NAb the immune system would be very ineffectual, while beyond some high value of NAb further increases in NAb yield diminishing small increases in P. Multispecificity is equivalent to a modest increase (probably less than 10) in the antibody repertoire size NAb, but this increase can substantially improve the probability of an immune system recognizing a foreign molecule. Besides recognizing foreign molecules, the immune system must distinguish them from self molecules. Using the mathematical theory of reliability multisite recognition is a more reliable method of distinguishing between molecules than single site recognition. This may have been an important evolutionary consideration in the selection of weak non-covalent interactions as the basis of antigen-antibody bonds.