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外源性抗原蛋白被抗原提呈细胞(APC)摄取送入溶酶体中被降解为长度不一的肽段.在HLA-DM分子辅助下,MHC II类分子相关恒定链多肽(class II-associated invariant chain peptide,CLIP)从MHC II类分子的肽结合槽解离,使得外源性抗原降解的肽段进入MHC II类分子空的肽结合槽中,形成稳定的抗原肽-MHC II类分子复合物.之后再被提呈到APC细胞表面供CD4+Th细胞的TCR识别,激活Th细胞分泌细胞因子,促进CTL细胞特异性杀伤靶细胞或辅助B细胞产生抗体.Th细胞的活化对机体的细胞免疫和体液免疫功能都有重要的辅助作用.本工作基于迭代自洽策略与支持向量回归机(ISC-SVR)方法建立了MHC II类分子与外源性抗原肽结合亲合力预测模型,采用13mer扩展核心结合序列可以提高预测模型的性能,分别按照均值法、最大值法、结合法、加权平均值法4种方法计算MHC II类分子与抗原肽的结合亲合力值.对17种MHC II类分子配型进行了回归分析,与其他预测模型相比较,本工作模型都得到了最佳AUC值.最后,以HLA DRB1*0101分子为例,分析讨论了MHC II类分子与抗原肽的结合特异性.
Exogenous antigenic proteins are taken up by antigen presenting cells (APCs) into peptides that are degraded to varying lengths in lysosomes, and HLA class II molecules with the help of HLA class II molecules, class II- associated invariant chain peptide (CLIP) is dissociated from the peptide binding groove of the MHC class II molecule such that the exogenous antigen-degraded peptide enters the empty peptide binding groove of the MHC class II molecule to form a stable antigenic peptide, an MHC class II molecule Complex and then be presented to APC cell surface for TCR recognition of CD4 + Th cells, activate Th cells to secrete cytokines, and promote CTL cell-specific killing of target cells or helper B cells to produce antibodies .Th cell activation on the body Cellular immunity and humoral immune function.It is based on the iterative self-consistent strategy and support vector regression (ISC-SVR) method to establish the prediction model of binding affinity between MHC class II molecules and exogenous antigen peptide, 13mer extension of the core binding sequence can improve the performance of the predictive model, respectively, according to the average method, the maximum value method, the binding method, the weighted average method four methods to calculate the binding affinity of MHC class II molecules and antigen peptides .For 17 kinds of MHC Class II molecules were analyzed by regression analysis.Compared with other prediction models, the best AUC value was obtained in this model.Finally, taking HLA DRB1 * 0101 as an example, we analyzed the relationship between MHC class II molecules and antigenic peptides Binding specificity.