Wieczorek Marek, Abualrous Esam T, Sticht Jana, Álvaro-Benito Miguel, Stolzenberg Sebastian, Noé Frank, Freund Christian
Protein Biochemistry, Institute for Biochemistry, Freie Universität Berlin , Berlin , Germany.
Computational Molecular Biology Group, Institute for Mathematics , Berlin , Germany.
Front Immunol. 2017 Mar 17;8:292. doi: 10.3389/fimmu.2017.00292. eCollection 2017.
Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell's own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response. Once processed, the peptide repertoire presented by MHC proteins largely depends on structural features of the binding groove of each particular MHC allelic variant. Additionally, two peptide editors-tapasin for class I and HLA-DM for class II-contribute to the shaping of the presented peptidome by favoring the binding of high-affinity antigens. Although there is a vast amount of biochemical and structural information, the mechanism of the catalyzed peptide exchange for MHC class I and class II proteins still remains controversial, and it is not well understood why certain MHC allelic variants are more susceptible to peptide editing than others. Recent studies predict a high impact of protein intermediate states on MHC allele-specific peptide presentation, which implies a profound influence of MHC dynamics on the phenomenon of immunodominance and the development of autoimmune diseases. Here, we review the recent literature that describe MHC class I and II dynamics from a theoretical and experimental point of view and we highlight the similarities between MHC class I and class II dynamics despite the distinct functions they fulfill in adaptive immunity.
主要组织相容性复合体（MHC）蛋白介导的抗原呈递对于适应性免疫至关重要。在呈递之前，肽需要从细胞自身翻译机制产生的蛋白质或进入内溶酶体囊泡系统的蛋白质中生成。在二级淋巴器官中经过广泛搜索过程后，T细胞受体与特定的肽-MHC复合物之间的长时间相互作用最终触发T细胞增殖并引发特异性细胞免疫反应。一旦加工完成，MHC蛋白呈递的肽库很大程度上取决于每个特定MHC等位基因变体结合槽的结构特征。此外，两种肽编辑蛋白——I类的塔帕辛和II类的HLA-DM——通过促进高亲和力抗原的结合，有助于塑造呈递的肽组。尽管有大量的生化和结构信息，但I类和II类MHC蛋白催化的肽交换机制仍存在争议，而且对于某些MHC等位基因变体比其他变体更容易受到肽编辑的影响的原因也尚未完全理解。最近的研究预测蛋白质中间状态对MHC等位基因特异性肽呈递有很大影响，这意味着MHC动力学对免疫优势现象和自身免疫性疾病的发展有深远影响。在这里，我们从理论和实验的角度回顾了描述I类和II类MHC动力学的最新文献，并强调了I类和II类MHC动力学之间的相似性，尽管它们在适应性免疫中发挥着不同的功能。
