Dapeng Zhou¹, Steven B. Levery², Fong-Fu Hsu³, Peng G. Wang⁴, Susann Teneberg⁵, Igor C. Almeida⁶, Yunsen Li⁷, Huaxi Xu⁸, Lai-Xi Wang⁹, Chengfeng Xia¹⁰, Nuhad K Ibrahim¹¹, Katja Michael¹²

1Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77054, USA, ²Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark, ³Mass Spectrometry Resource, Division of Endocrinology, Diabetes, Metabolism, and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA, ⁴Department of Biochemistry, The Ohio State University, Columbus, OH 43210, ⁵Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, S-40530 Göteborg, Sweden, ⁶Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, ⁷Institute of Biological and Medical Sciences, Medical College, Soochow University, Suzhou 215123, China, ⁸School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212001, China, ⁹Institute of Human Virology and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, Baltimore, MA 21201, ¹⁰State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China, ¹¹Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, ¹²Department of Chemistry, University of Texas at El Paso, El Paso, TX 79968

TABLE OF CONTENTS

1. Abstract

2. Introduction

2.1. The role of immune receptors as signal sensors in both innate and adaptive immunity

2.2. The impact of immune receptor signaling on biology of immune cells

3. Immunobiology of receptors recognizing glycoconjugates

3.1. C-type lectins, Siglecs, galectins, and other animal lectins

3.2. B cell receptors

3.3. Special concerns for glycoconjugate-specific antibodies

3.4. T cell receptors for glycans

4. Genetics and biochemistry for glycan immune epitopes

4.1. Glycoproteins and glycolipids are metabolically unique and structurally challenging

4.2. Gene chips and microarrays cannot be used to detect glycan epitopes

4.3. Assembly of glycan immune epitopes in unique cellular compartments

4.4. Conventional biochemical purification approach for immune epitope discovery

4.5. Limitations of conventional biochemical purification approach

5. Proposing, testing and verifying hypothetical glycan immune epitopes

5.1. Why hypothetical epitopes

5.2. Interdisciplinary nature of immunologic glycomics: synergized efforts by immunobiology, analytical chemistry, and synthetic chemistry

6. Essential role of analytical methods and tools in the hypothesis-generating phase

6.1. Ion trap mass spectrometry as a unique tool in glycomics and lipidomics study

6.2. Sample preparation and separation technology

6.3. Controversies on the detection of immune epitopes in low abundance

7. Early insight into clinical applications

7.1. Demands and markets

7.2. Future directions

7.3. Five-year view

8. Acknowledgements

9. References

1. ABSTRACT