Human antibody responses are established by the generation of combinatorial sequence diversity in antibody variable domains, followed by iterative rounds of mutation and selection via T cell recognition of antigen peptides presented on MHC-II. Here, we report that MHC-II peptide epitope deletion from B cell receptors (BCRs) correlates with antibody development in vivo. Large-scale antibody sequence analysis and experimental validation of peptide binding revealed that MHC-II epitope removal from BCRs is linked to genetic signatures of T cell help, and donor-specific antibody repertoire modeling demonstrated that somatic hypermutation selectively targets the personalized MHC-II epitopes in antibody variable regions. Mining of class-switched sequences and serum proteomic data revealed that MHC-II epitope deletion is associated with antibody class switching and long-term secretion into serum. These data suggest that the MHC-II peptide epitope content of a BCR is an important determinant of antibody maturation that shapes the composition and durability of humoral immunity.

中文翻译：

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通过选择性去除MHC-II肽表位来个性化人类抗体的免疫反应

通过在抗体可变域中产生组合序列多样性，然后通过T细胞识别MHC-II抗原肽的T细胞识别，进行反复的突变和选择，从而建立人抗体反应。在这里，我们报道从B细胞受体（BCR）的MHC-II肽表位缺失与体内抗体的发展有关。大规模抗体序列分析和肽结合的实验验证表明，从BCR中去除MHC-II表位与T细胞帮助的遗传特征有关，而供体特异性抗体库模型表明，体细胞超突变选择性地针对了个性化MHC-II表位在抗体可变区中。分类转换序列和血清蛋白质组数据的挖掘表明，MHC-II表位缺失与抗体分类转换和长期分泌到血清中有关。这些数据表明，BCR的MHC-II肽表位含量是抗体成熟的重要决定因素，抗体成熟决定了体液免疫的组成和持久性。