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Immunity evolves as a powerful defense system to protect organisms from pathogens. Based on the different types of lymphocytes, immunity is divided into two categories: cell-mediated immunity and humoral immunity, which are regulated by T cells and B cells, respectively. These two types of immune responses are common in that they are stimulated by recognitions of antigen through specific receptors, termed T cell receptor (TCR) and antibodies. In cell-mediated immunity, glycolipids represent a distinctive type of antigens to activate natural killer T (NKT) cells when presented by Cluster of Differentiation 1 (CD1) proteins. The ability of rapidly producing large quantities of interferons and interleukins make NKT cells important targets for understanding the initiation and regulation of various immune responses, as well as the development of potential immunotherapy. Discoveries of the most potent ligand α-galactosylceramide (α-GalCer) and the endogenous ligand isoglobotrihexosylceramide (iGb3) have spurred an enthusiastic pursue of optimized glycolipid candidates for potential therapeutic applications. Herein, one of my research projects was to use chemical modifications as probes to explore the interactions among CD1d, glycolipid and the T cell receptor (TCR). These studies provided an insight into the structural requirements for natural endogenous ligand (iGb3) for NKT cells activation. In addition, an oxime ligation strategy was successfully developed to generate novel analogues of α-GalCer. This achievement demonstrated a more efficient and concise way to obtain varied glycolipid analogues than traditional glycosylation methods, and would help to expand current glycolipids library for discovery of potential glycolipid candidates. Furthermore, computer-assisted drug design was initiated to discover novel non-glycosylated ceramide lipids for NKT cells. An efficient synthetic design was carried out to produce a small library of glycolipid mimics. On the other hand, carbohydrates play crucial roles in humoral immunity in that many carbohydrate epitopes are identified as antigens for antibodies. In order to obtain therapeutically effective carbohydrate-based vaccine, we developed efficient and practical syntheses of glycoproteins with varied carbohydrate antigens, including α-Gal, Rha monosaccharide and Forssman disaccharide. The critical technology in this project involved the development of efficient activation of varied carboxylic acid linkers with N,N,N′,N′-tetramethyl (succinimido) uronium tetrafluoroborate (TSTU). In addition, both synthetic α-Gal-conjugated protein and Rha-conjugated proteins exhibited intact biological function during our antibody recognition and mice immunization experiments. Overall, our demonstrated strategy provides a useful probe for the future carbohydrate based vaccine development.Daunorubicin is an effective anticancer drug used in leukemia and lymphoma. Recent studied suggested that altering the structure of carbohydrate portion is able to overcome its limitations, such as drug resistance and cardiotoxicity. To further understand the SAR of sugar moiety on daunorubicin’s anticancer activity, six α-linked daunorbucin monosaccharides were stereoselectively synthesized and biologically evaluated. It was revealed that modifications on the sugar moiety resulted in the fluctuation of the anthracycline’s activity. The introduction of axial-3'-substituent on sugar may interfere with binding to DNA, while 4'-OH is critical for anticancer activity. Our SAR study suggested that 2,6-dideoxy sugars are the best choices of uncommon sugars for daunorubicin in comparison with 6-deoxy, 2,3,6-trideoxy, and 2,3,4,6-tetradeoxy sugars.