各种不同的糖基结构覆盖在所有的细胞表面上，并参与无数的生物过程，其中包括但不限于：细胞黏附、信号传导、代谢、蛋白质质量控制以及与先天和适应性免疫功能紧密相关。免疫监测和对外源性碳水化合物抗原的反应（例如细菌包被多糖和病毒表面蛋白糖基化），是微生物清除的基础，大部分抗微生物疫苗都以这些结构为靶点。此外，肿瘤上异常糖基被称为肿瘤相关糖抗原（TACAs），它们会引起免疫反应并用于抗肿瘤疫苗的设计。哺乳动物绝大部分TACAs都来源于所谓的黏液型O-糖基化的细胞表面蛋白，并通过丝氨酸或苏氨酸残基的羟基与蛋白质骨架相连接。一些单糖和寡糖附着在这些残基上的结构研究显示，附着在“未甲基化”的丝氨酸或苏氨酸β-甲基化残基上的糖基的构象偏好存在显著差异。这表明抗原糖基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（例如凝集素）的展示方式。本文将研究这种可能性，并把概念扩展到表面和测定系统中的糖基展示，这些展示将由不同的连接点来定义，从而产生各种不同的构象表现。版权所有 © 2023 Barchi and Strain.

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 ß-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.Copyright © 2023 Barchi and Strain.