Barchi Joseph J, Strain Caitlin N
Center for Cancer Research, Chemical Biology Laboratory, National Cancer Institute at Frederick, Frederick, MD, United States.
Front Mol Biosci. 2023 Feb 10;10:1117850. doi: 10.3389/fmolb.2023.1117850. eCollection 2023.
A variety of glycan structures cover the surface of all cells and are involved in myriad biological processes, including but not limited to, cell adhesion and communication, protein quality control, signal transduction and metabolism, while also being intimately involved in innate and adaptive immune functions. Immune surveillance and responses to foreign carbohydrate antigens, such as capsular polysaccharides on bacteria and surface protein glycosylation of viruses, are the basis of microbial clearance, and most antimicrobial vaccines target these structures. In addition, aberrant glycans on tumors called Tumor-Associated Carbohydrate Antigens (TACAs) elicit immune responses to cancer, and TACAs have been used in the design of many antitumor vaccine constructs. A majority of mammalian TACAs are derived from what are referred to as mucin-type O-linked glycans on cell-surface proteins and are linked to the protein backbone through the hydroxyl group of either serine or threonine residues. A small group of structural studies that have compared mono- and oligosaccharides attached to each of these residues have shown that there are distinct differences in conformational preferences assumed by glycans attached to either "unmethylated" serine or -methylated threonine. This suggests that the linkage point of antigenic glycans will affect their presentation to the immune system as well as to various carbohydrate binding molecules (e.g., lectins). This short review, followed by our hypothesis, will examine this possibility and extend the concept to the presentation of glycans on surfaces and in assay systems where recognition of glycans by proteins and other binding partners can be defined by different attachment points that allow for a range of conformational presentations
各种各样的聚糖结构覆盖在所有细胞表面，并参与无数生物过程，包括但不限于细胞黏附与通讯、蛋白质质量控制、信号转导与代谢，同时也密切参与固有免疫和适应性免疫功能。免疫监视以及对外源碳水化合物抗原（如细菌的荚膜多糖和病毒的表面蛋白糖基化）的反应是微生物清除的基础，大多数抗菌疫苗都针对这些结构。此外，肿瘤上的异常聚糖，即肿瘤相关碳水化合物抗原（TACAs），引发对癌症的免疫反应，并且TACAs已被用于许多抗肿瘤疫苗构建体的设计中。大多数哺乳动物TACAs源自细胞表面蛋白上所谓的粘蛋白型O-连接聚糖，并通过丝氨酸或苏氨酸残基的羟基与蛋白质主链相连。少数比较连接到每个这些残基上的单糖和寡糖的结构研究表明，连接到“未甲基化”丝氨酸或甲基化苏氨酸上的聚糖所呈现的构象偏好存在明显差异。这表明抗原聚糖的连接点将影响它们向免疫系统以及各种碳水化合物结合分子（如凝集素）的呈现。这篇简短的综述，接着是我们的假设，将探讨这种可能性，并将这一概念扩展到表面聚糖以及检测系统中的聚糖呈现，在这些系统中，蛋白质和其他结合伴侣对聚糖的识别可以由不同的连接点来定义，从而允许一系列构象呈现
