The nonclassical major histocompatibility complex of class II molecules (ncMHCII) HLA‐DM (DM) and HLA‐DO (DO) feature essential functions for the selection of the peptides that are displayed by classical MHCII proteins (MHCII) for CD4⁺ T_h cell surveillance. Thus, although the binding groove of classical MHCII dictates the main features of the peptides displayed, ncMHCII function defines the preferential loading of peptides from specific cellular compartments and the extent to which they are presented. DM acts as a chaperone for classical MHCII molecules facilitating peptide exchange and thereby favoring the binding of peptide‐MHCII complexes of high kinetic stability mostly in late endosomal compartments. DO on the other hand binds to DM blocking its peptide‐editing function in B cells and thymic epithelial cells, limiting DM activity in these cellular subsets. DM and DO distinct expression patterns therefore define specific antigen presentation profiles that select unique peptide pools for each set of antigen presenting cell. We have come a long way understanding the mechanistic underpinnings of such distinct editing profiles and start to grasp the implications for ncMHCII biological function. DM acts as filter for the selection of immunodominant, pathogen‐derived epitopes while DO blocks DM activity under certain physiological conditions to promote tolerance to self. Interestingly, recent findings have shown that the unexplored and neglected ncMHCII genetic diversity modulates retroviral infection in mouse, and affects human ncMHCII function. This review aims at highlighting the importance of ncMHCII function for CD4⁺ T_h cell responses while integrating and evaluating what could be the impact of distinct editing profiles because of natural genetic variations.

中文翻译：

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回顾非经典HLA II在抗原呈递中的功能：肽编辑及其调节。

II类分子（ncMHCII）HLA-DM（DM）和HLA-DO（DO）的非经典主要组织相容性复合物具有选择经典MHCII蛋白（MHCII）显示的CD4 ⁺ T _h肽段的基本功能细胞监视。因此，尽管经典MHCII的结合槽决定了所展示肽的主要特征，但是ncMHCII功能定义了来自特定细胞区室的肽的优先负载及其呈现的程度。DM充当经典MHCII分子的分子伴侣，可促进肽交换，从而有利于在后期的内体区室中结合具有高动力学稳定性的肽-MHCII复合物。另一方面，DO与DM结合，阻止DM在B细胞和胸腺上皮细胞中的肽编辑功能，从而限制了这些细胞亚群中的DM活性。因此，DM和DO不同的表达模式定义了特异性抗原呈递谱，其为每组抗原呈递细胞选择独特的肽库。我们已经走了很长一段路要理解这种不同的编辑配置文件的机制基础，并开始掌握对ncMHCII生物学功能的含义。DM充当筛选免疫原性，病原体来源表位的筛选器，而DO在某些生理条件下会阻断DM活性，从而增强自我耐受性。有趣的是，最近的发现表明，尚未开发且被忽视的ncMHCII遗传多样性可调节小鼠的逆转录病毒感染，并影响人类ncMHCII的功能。这篇综述旨在强调ncMHCII功能对CD4的重要性 病原体衍生的抗原决定簇，而DO在某些生理条件下会阻止DM活性，从而增强自我耐受性。有趣的是，最近的发现表明，尚未开发且被忽视的ncMHCII遗传多样性可调节小鼠的逆转录病毒感染，并影响人类ncMHCII的功能。这篇综述旨在强调ncMHCII功能对CD4的重要性 病原体衍生的抗原决定簇，而DO在某些生理条件下会阻止DM活性，从而增强自我耐受性。有趣的是，最近的发现表明，尚未开发且被忽视的ncMHCII遗传多样性可调节小鼠的逆转录病毒感染，并影响人类ncMHCII的功能。这篇综述旨在强调ncMHCII功能对CD4的重要性⁺ T _h细胞反应，同时整合和评估由于自然遗传变异而可能对不同编辑谱产生的影响。