McKitrick Tanya R, Eris Deniz, Mondal Nandini, Aryal Rajindra P, McCurley Nathanael, Heimburg-Molinaro Jamie, Cummings Richard D
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, National Center for Functional Glycomics, CLS 11087-3 Blackfan Circle, Boston, Massachusetts 02115, United States.
Office of Technology Transfer and Commercialization, Georgia State University, 58 Edgewood Ave Rm 341, Atlanta, Georgia 30303, United States.
Biochemistry. 2020 Sep 1;59(34):3111-3122. doi: 10.1021/acs.biochem.9b01015. Epub 2020 Feb 27.
The repertoire of glycans expressed by individual cells and tissues is enormous, and various estimates indicate that thousands of different glycans and "glycan determinants" are critical for functional recognition by glycan-binding proteins. Defining the steady-state expression and functional impacts of the human glycome will require a concerted worldwide effort, along with the development of new immunological, genetic, chemical, and biochemical technologies. Here, we describe the generation of smart anti-glycan reagents (SAGRs), recombinant antibodies that recognize novel glycan determinants. The antibodies are generated by the sea lamprey (), through immunization with glycoconjugates, cells, and even tissues. SAGRs represent a versatile immunological tool for defining the expression of glycans in cells and tissues. We also present a comparison of lamprey-derived anti-carbohydrate antibodies that have been characterized to date. Finally, we explore the unique glyco-genome of the lamprey itself as it compares to those of humans and mice and how it may relate to the lamprey's inherent capacity to produce antibodies to mammalian glycans.
单个细胞和组织所表达的聚糖种类繁多,各种估计表明,数千种不同的聚糖和“聚糖决定簇”对于聚糖结合蛋白的功能识别至关重要。定义人类糖组的稳态表达和功能影响需要全球共同努力,同时还需要开发新的免疫学、遗传学、化学和生物化学技术。在这里,我们描述了智能抗聚糖试剂(SAGR)的产生,即识别新型聚糖决定簇的重组抗体。这些抗体是通过用糖缀合物、细胞甚至组织免疫海七鳃鳗产生的。SAGR是一种用于定义细胞和组织中聚糖表达的通用免疫学工具。我们还对迄今为止已鉴定的七鳃鳗来源的抗碳水化合物抗体进行了比较。最后,我们探讨了七鳃鳗自身独特的糖基因组与人类和小鼠的糖基因组相比情况,以及它与七鳃鳗产生针对哺乳动物聚糖抗体的内在能力之间的关系。