Mechanical, Aerospace, and Biomedical Engineering Department, University of Tennessee, Knoxville, TN 37996, USA.
Math Biosci. 2010 May;225(1):53-8. doi: 10.1016/j.mbs.2010.01.009. Epub 2010 Feb 4.
Immunodominance is a common phenomenon observed in multiple epitopes immune systems. Previous studies hypothesize that the competition among CD8+ T cell responses against different epitopes can be used to explain immunodominance. This paper proposes a mathematical model that describes the dynamics of CD8+ T cells primed by antigen-presenting dendritic cells (DCs) in the lymph nodes, and shows that the overall avidity of the interactions between peptide-specific T cells and cognate antigen-bearing DCs may determine the immunodominance. The model suggests the probability that a peptide-specific T cell be immunodominant is proportional to (1) the cognate T cell receptor (TCR) affinity, (2) the number of complexes of cognate peptide and major histocompatibility complex (pMHC) per DC, and (3) the half-life of cognate peptide-specific pMHC. The model predicts a threshold density of pMHC complexes for T cell activation. These observations from the mathematical model are consistent with experimental studies in the open literature. For DC-based vaccine design, the model suggests a strategy of immunotherapy based on the injection of cognate antigen-pulsed DCs.
优势免疫是在多个表位免疫系统中观察到的一种常见现象。先前的研究假设，针对不同表位的 CD8+ T 细胞反应之间的竞争可以用来解释优势免疫。本文提出了一个数学模型，描述了在淋巴结中由抗原呈递树突状细胞 (DC) 引发的 CD8+ T 细胞的动力学，表明肽特异性 T 细胞与同源抗原结合的 DC 之间相互作用的整体亲和力可能决定优势免疫。该模型表明，肽特异性 T 细胞成为优势免疫的概率与以下因素成正比：(1) 同源 T 细胞受体 (TCR) 亲和力；(2) 每个 DC 中同源肽和主要组织相容性复合物 (pMHC) 的复合物数量；(3) 同源肽特异性 pMHC 的半衰期。该模型预测了 T 细胞激活的 pMHC 复合物的临界密度。这些来自数学模型的观察结果与文献中的实验研究一致。对于基于 DC 的疫苗设计，该模型提出了一种基于注射同源抗原脉冲化 DC 的免疫疗法策略。
