Nowak M A, May R M, Sigmund K
Department of Zoology, University of Oxford, U.K.
J Theor Biol. 1995 Aug 7;175(3):325-53. doi: 10.1006/jtbi.1995.0146.
The current understanding of antigenic escape dynamics is based on models with single epitopes. The usual idea is that a mutation which enables a pathogen (virus, bacteria, etc) to escape from a given immune response confers a selective advantage. The "escape mutant" may then increase in abundance until it induces a new specific response against itself. In this paper a new picture is developed, based on mathematical models of immune responses against several epitopes; the simplest such models can have very complicated dynamics, with some surprising features. The emergence of an escape mutant can shift the immunodominant response to another epitope. Even in the absence of mutations, antigenic oscillation is found, with distinct peaks of different virus variants and fluctuations in the size and specificity of the immune responses. The model also provides a general theory for immunodominance in the presence of antigenic variation. Immunodominance is determined by the immunogenicity and by the antigenic diversity of the competing epitopes. Antigenic oscillations and fluctuations in the cytotoxic T-lymphocyte response have been observed in infections with the human immunodeficiency virus (HIV). Shifting the immune responses to weaker epitopes can represent a mechanism for disease progression based on evolutionary dynamics and antigenic diversity of the virus.
目前对抗原逃逸动力学的理解是基于单表位模型。通常的观点是，使病原体（病毒、细菌等）能够逃避特定免疫反应的突变赋予了一种选择优势。然后，“逃逸突变体”的数量可能会增加，直到它引发针对自身的新的特异性反应。在本文中，基于针对多个表位的免疫反应数学模型，构建了一幅新的图景；最简单的此类模型可能具有非常复杂的动力学，带有一些惊人的特征。逃逸突变体的出现可将免疫显性反应转移至另一个表位。即使在没有突变的情况下，也会发现抗原振荡，不同病毒变体有明显的峰值，且免疫反应的规模和特异性存在波动。该模型还为存在抗原变异时的免疫显性提供了一个通用理论。免疫显性由竞争表位的免疫原性和抗原多样性决定。在人类免疫缺陷病毒（HIV）感染中已观察到细胞毒性T淋巴细胞反应中的抗原振荡和波动。将免疫反应转移至较弱的表位可能代表了一种基于病毒进化动力学和抗原多样性的疾病进展机制。
