An Introduction to Immunopeptidome

免疫肽组基础, Chinese translation available below.

The immunopeptidome refers to the repertoire of peptides bound and presented by major histocompatibility complex (MHC) molecules. These peptides provide an antigen pool recognized by T cells, some of which can elicit strong T cell responses the subsequent immunity.

The study of immunopeptidomics aims to explore immunogenetic epitopes. These epitopes play a crucial role in immune responses and serve as important targets for vaccine development or immunotherapy. For example, a 2019 clinical study published in Nature, titled “Actively personalized vaccination trial for newly diagnosed glioblastoma,” demonstrated the enormous potential of personalized vaccines developed based on immunopeptidome data in suppressing glioblastoma, a disease that is almost untreatable with checkpoint inhibitors.

The analysis of immunopeptidome can be briefly divided into the isolation and the measurement of immunopeptidomic samples. Isolation includes two optional methods: mild acid elution, which isolates peptides from intact cells; and immunoaffinity capture (IAC), which captures HLA molecules and their bound peptides from cell lysates using specific antibodies. The mainstream method for measurement is liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), where chromatography separates peptide mixtures and mass spectrometry determines peptide sequences.

Immunopeptidomics emerged from systems immunology whereas was made available through the joint efforts from multiple cutting-edge disciplines. The findings from immunopeptidomics not only contributes to breakthroughs in basic science but also provides new approaches for numerous clinical applications, such as the development of next-generation peptide vaccines and novel methods for disease monitoring.

免疫肽组(Immunopeptidome)是指由主要组织相容性复合体(MHC)分子结合并呈递的肽类的总和。这些肽类提供了一个抗原库供T细胞识别,其中一些肽类能够引发强烈的T细胞反应,进而启动后续的免疫反应。

在免疫肽组学的研究中,研究人员通过分析MHC分子呈递的肽类,探索免疫遗传表位。这些表位在免疫反应中扮演重要角色,是开发疫苗和免疫疗法的重要靶点。例如,2019年发表在Nature上的一项临床研究(Actively personalized vaccination trial for newly diagnosed glioblastoma),就展示了基于免疫肽组数据开发的个性化疫苗对于胶质母细胞瘤这种几乎无法用检查点抑制剂治疗的疾病的抑制具有巨大的潜力。

免疫肽组的分析流程可划分为免疫肽组样本的分离和检测。分离包括两种方法:温和酸洗法,从细胞裂解物、抗体或完整细胞中分离肽类​;免疫亲和捕获法(IAC):通过特异性抗体捕获HLA分子及其结合的肽类。检测的主流方法是液相色谱连接串联质谱法,其中色谱用于用于分离肽类混合物、而质谱用于确定肽的序列组成。

免疫肽组学催生于系统免疫学、而其研究的开展离不开多个前沿学科的共同努力。这一领域的研究不仅有助于基础科学的突破,也为诸多临床应用(新一代疫苗开发、疾病监测新方法等)带来了另外的思路​。

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