Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.

Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.
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DOI:
10.1002/pmic.202000143
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发表时间:
2021-12
期刊:
影响因子:
3.4
通讯作者:
Ternette N
Ternette N
中科院分区:
生物学3区
文献类型:
--
作者:
Joyce S;Ternette N

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T 细胞在针对多种感染和癌症的适应性免疫反应中发挥着重要作用。 T 细胞介导的免疫反应的启动需要在称为 MHC(主要组织相容性复合体)限制的过程中进行抗原识别。 T 细胞抗原是由结合在 MHC 编码的 I 类或 II 类分子的抗原结合沟内的肽片段组成的复合结构。深入了解自身和非自身免疫肽组的精确组成和生物学对于利用 T 细胞介导的免疫来预防、治疗或治愈传染病和癌症至关重要。 T细胞抗原的发现是一项艰巨的任务! 20 世纪 90 年代初的开创性工作使得大规模 T 细胞抗原发现成为可能。因此,质谱技术的进步与蛋白质组学和基因组学技术相结合,使得轻松、准确和灵敏地发现 T 细胞抗原成为可能。然而,我们才刚刚开始了解自体和非自体免疫肽组的广度和深度,因为细胞的分子生物学不断给我们带来与 MHC 配体的来源、加工和呈递直接相关的新秘密,让我们感到惊讶。因此,本综述以 MHC I 类分子为重点,提供了 T 细胞抗原发现的简要历史记录,并以分子细胞生物学过程的关键进展为背景,详细阐述了蛋白质基因组学方法如何彻底改变了该领域。
T cells play an important role in the adaptive immune response to a variety of infections and cancers. Initiation of a T cell mediated immune response requires antigen recognition in a process termed MHC (major histocompatibility complex) restri ction. A T cell antigen is a composite structure made up of a peptide fragment bound within the antigen‐binding groove of an MHC‐encoded class I or class II molecule. Insight into the precise composition and biology of self and non‐self immunopeptidomes is essential to harness T cell mediated immunity to prevent, treat, or cure infectious diseases and cancers. T cell antigen discovery is an arduous task! The pioneering work in the early 1990s has made large‐scale T cell antigen discovery possible. Thus, advancements in mass spectrometry coupled with proteomics and genomics technologies make possible T cell antigen discovery with ease, accuracy, and sensitivity. Yet we have only begun to understand the breadth and the depth of self and non‐self immunopeptidomes because the molecular biology of the cell continues to surprise us with new secrets directly related to the source, and the processing and presentation of MHC ligands. Focused on MHC class I molecules, this review, therefore, provides a brief historic account of T cell antigen discovery and, against a backdrop of key advances in molecular cell biologic processes, elaborates on how proteogenomics approaches have revolutionised the field.
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