The main objective of antigen processing is to orchestrate the selection of immunodominant epitopes for recognition by CD4 T cells. To achieve this, MHC class II molecules have evolved with a flexible peptide-binding groove in need of a bound peptide. Newly synthesized MHC-II molecules bind a class II invariant chain (Ii) upon synthesis and are shuttled to a specialized compartment, where they encounter exogenous antigens. Ii serves multiple functions, one of which is to maintain the shape of the MHC-II groove so that it can readily bind exogenous antigens upon dissociation of the Ii peptide in MHC- II compartment. MIIC contains processing enzymes, one or both accessory molecules, HLA-DM/H2-M (DM) and HLA-DO/H2-O (DO), and optimal denaturing conditions. In a process known as "editing," DM facilitates the dissociation of the invariant chain peptide, CLIP, for exchange with exogenous antigens. Despite the availability of mechanistic insights into DM functions, understanding how DO contributes to epitope selection has proven to be more challenging. The current dogma assumes that DO inhibits DM, whereas an opposing model suggests that DO fine-tunes the epitope selection process. Understanding which of these, or potentially other models of DO function is important, as DO variants have been linked to autoimmunity, cancer, and the generation of broadly neutralizing antibodies to viruses. This review therefore attempts to evaluate experimental evidence in support of these hypotheses, with an emphasis on the less discussed model, and to explore intriguing questions about the importance of DO in biology.

中文翻译：

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二十年后，HLA-DO/H-2O 该怎么办？


抗原加工的主要目的是协调选择免疫显性表位以供 CD4 T 细胞识别。为了实现这一目标，MHC II 类分子进化出了需要结合肽的灵活肽结合槽。新合成的 MHC-II 分子在合成时结合 II 类不变链 (Ii)，并穿梭到专门的区室，在那里它们遇到外源抗原。 Ii 具有多种功能，其中之一是维持 MHC-II 凹槽的形状，以便在 Ii 肽在 MHC-II 区室中解离时能够轻松结合外源抗原。 MIIC 包含加工酶、一种或两种辅助分子、HLA-DM/H2-M (DM) 和 HLA-DO/H2-O (DO) 以及最佳变性条件。在称为“编辑”的过程中，DM 促进恒定链肽 CLIP 的解离，以便与外源抗原进行交换。尽管可以深入了解 DM 功能的机制，但了解 DO 如何促进表位选择已被证明更具挑战性。当前的教条假设 DO 抑制 DM，而相反的模型表明 DO 微调表位选择过程。了解这些模型或潜在的其他 DO 功能模型很重要，因为 DO 变异与自身免疫、癌症以及病毒广泛中和抗体的产生有关。因此，本综述试图评估支持这些假设的实验证据，重点是讨论较少的模型，并探讨有关溶解氧在生物学中的重要性的有趣问题。