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Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies.

ABSTRACT: Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development.

SUBMITTER: Gildersleeve JC

PROVIDER: S-EPMC3478784 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies.

Gildersleeve Jeffrey C JC Wang Baomei B Achilefu Samuel S Tu Zhude Z Xu Mai M

Bioorganic & medicinal chemistry letters 20120924 22

Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The an ...[more]

PMID: 23063402

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Project description:Gut commensal bacteria are known to have a significant role in regulating the innate and adaptive immune homeostasis. Alterations in the intestinal microbial composition have been associated with several disease states, including autoimmune and inflammatory conditions. However, it is not entirely clear how commensal gut microbiota modulate and contribute to the systemic immunity, and whether circulating elements of the host immune system could regulate the microbiome. Thus, we have studied the diversity and abundance of specific taxons in the gut microbiota of inbred GalT-KO mice during 7 months of animal life by metagenetic high-throughput sequencing (16S rRNA gene, variable regions V3-V5). The repertoire of glycan-specific natural antibodies, obtained by printed glycan array technology, was then associated with the microbial diversity for each animal by metagenome-wide association studies (MWAS). Our data show that the orders clostridiales (most abundant), bacteriodales, lactobacillales, and deferribacterales may be associated with the development of the final repertoire of natural anti-glycan antibodies in GalT-KO mice. The main changes in microbiota diversity (month-2 and month-3) were related to important changes in levels and repertoire of natural anti-glycan antibodies in these mice. Additionally, significant positive and negative associations were found between the gut microbiota and the pattern of specific anti-glycan antibodies. Regarding individual features, the gut microbiota and the corresponding repertoire of natural anti-glycan antibodies showed differences among the examined animals. We also found redundancy in different taxa associated with the development of specific anti-glycan antibodies. Differences in microbial diversity did not, therefore, necessarily influence the overall functional output of the gut microbiome of GalT-KO mice. In summary, the repertoire of natural anti-carbohydrate antibodies may be partially determined by the continuous antigenic stimulation produced by the gut bacterial population of each GalT-KO mouse. Small differences in gut microbiota diversity could determine different repertoire and levels of natural anti-glycan antibodies and consequently might induce different immune responses to pathogens or other potential threats.

Dataset Information

Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies.

Publications

Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies.

Similar Datasets

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