Purcell A W, Gorman J J
Department of Microbiology and Immunology and ImmunoID, The University of Melbourne, Victoria 3010, Australia.
Mol Cell Proteomics. 2004 Mar;3(3):193-208. doi: 10.1074/mcp.R300013-MCP200. Epub 2004 Jan 12.
The mammalian immune system has evolved to display fragments of protein antigens derived from microbial pathogens to immune effector cells. These fragments are typically peptides liberated from the intact antigens through distinct proteolytic mechanisms that are subsequently transported to the cell surface bound to chaperone-like receptors known as major histocompatibility complex (MHC) molecules. These complexes are then scrutinized by effector T cells that express clonally distributed T cell receptors with specificity for specific MHC-peptide complexes. In normal uninfected cells, this process of antigen processing and presentation occurs continuously, with the resultant array of self-antigen-derived peptides displayed on the surface of these cells. Changes in this peptide landscape of cells act to alert immune effector cells to changes in the intracellular environment that may be associated with infection, malignant transformation, or other abnormal cellular processes, resulting in a cascade of events that result in their elimination. Because peptides play such a crucial role in informing the immune system of infection with viral or microbial pathogens and the transformation of cells in malignancy, the tools of proteomics, in particular mass spectrometry, are ideally suited to study these immune responses at a molecular level. Here we review recent advances in the studies of immune responses that have utilized mass spectrometry and associated technologies, with specific examples from collaboration between our laboratories.
哺乳动物的免疫系统已经进化到能够将源自微生物病原体的蛋白质抗原片段展示给免疫效应细胞。这些片段通常是通过独特的蛋白水解机制从完整抗原中释放出来的肽段，随后被转运到细胞表面，并与称为主要组织相容性复合体（MHC）分子的伴侣样受体结合。然后，效应T细胞会对这些复合物进行检查，这些效应T细胞表达具有克隆分布且对特定MHC-肽复合物具有特异性的T细胞受体。在未感染的正常细胞中，抗原加工和呈递过程持续发生，这些细胞表面会展示出一系列源自自身抗原的肽段。细胞中这种肽谱的变化会提醒免疫效应细胞细胞内环境可能发生了与感染、恶性转化或其他异常细胞过程相关的变化，从而引发一系列导致这些细胞被清除的事件。由于肽段在向免疫系统通报病毒或微生物病原体感染以及细胞恶性转化方面起着至关重要的作用，蛋白质组学工具，尤其是质谱技术，非常适合在分子水平上研究这些免疫反应。在此，我们回顾利用质谱技术及相关技术进行免疫反应研究的最新进展，并给出我们实验室合作的具体实例。
