DO (HLA-DO, in human; murine H2-O) is a highly conserved nonclassical major histocompatibility complex class II (MHC II) accessory molecule mainly expressed in the thymic medulla and B cells. Previous reports have suggested possible links between DO and autoimmunity, Hepatitis C (HCV) infection, and cancer, but the mechanism of how DO contributes to these diseases remains unclear. Here, using a combination of various in vivo approaches, including peptide elution, mixed lymphocyte reaction, T-cell receptor (TCR) deep sequencing, tetramer-guided naïve CD4 T-cell precursor enumeration, and whole-body imaging, we report that DO affects the repertoire of presented self-peptides by B cells and thymic epithelium. DO induces differential effects on epitope presentation and thymic selection, thereby altering CD4 T-cell precursor frequencies. Our findings were validated in two autoimmune disease models by demonstrating that lack of DO increases autoreactivity and susceptibility to autoimmune disease development.

中文翻译：

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MHC II类分子伴侣H2-O的缺乏会导致自身免疫性疾病的易感性。

DO（人类中的HLA-DO；鼠类H2-O）是高度保守的非经典主要组织相容性复合体II类（MHC II）辅助分子，主要在胸腺髓质和B细胞中表达。先前的报告表明溶解氧与自身免疫，丙型肝炎（HCV）感染和癌症之间可能存在联系，但溶解氧如何促成这些疾病的机制仍不清楚。在此，我们结合使用多种体内方法，包括肽洗脱，混合淋巴细胞反应，T细胞受体（TCR）深度测序，四聚体引导的纯净CD4 T细胞前体计数和全身成像，我们报道了DO通过B细胞和胸腺上皮细胞影响所呈递的自身肽库。DO诱导对抗原决定簇呈递和胸腺选择的不同作用，从而改变CD4 T细胞前体的频率。