Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response
2012
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- Autor(en) / Beteiligte
- Titel
- Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response
- Ist Teil von
- PloS one, 2012-11, Vol.7 (11), p.e50139
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (HLA-A2 transgenic) mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0050139Titel-ID: cdi_plos_journals_1350900173
- Format
- –
- Schlagworte
- Aberration, Acetylgalactosamine - metabolism, Albumin, Amino Acid Sequence, Animals, Antibody response, Antibody Specificity - immunology, Antigen presentation, Antigen Presentation - immunology, Antigen processing, Antigens, Antigens, Neoplasm - immunology, Biology, Cancer, Cancer immunotherapy, Cancer treatment, Carcinogenesis, Carcinogens, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, CD8 antigen, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Cell Line, Cell proliferation, Cytotoxicity, Dendritic cells, Genetic engineering, Glycosylation, Health sciences, Histocompatibility antigen HLA, Histocompatibility Antigens Class I - immunology, Histocompatibility Antigens Class I - metabolism, HLA antigens, Immune response, Immune system, Immunization, Immunoglobulin G - immunology, Immunoglobulins, Immunology, Immunotherapy, Interferon, Interleukin 2, Lectins, Lymphocyte Activation - immunology, Lymphocytes, Lymphocytes T, Major histocompatibility complex, Medicine, MHC antibodies, Mice, Molecular Sequence Data, MUC-1 antigen, Mucin, Mucin-1 - chemistry, Mucin-1 - immunology, Mucin-1 - metabolism, Mucins, Neoplasms - immunology, Neoplasms - metabolism, Ovalbumin, Peptides, Peptides - chemistry, Peptides - metabolism, Polypeptides, Polysaccharides, Protein Binding - immunology, Proteins, T cells, Transgenic animals, Transgenic mice, Vaccines, γ-Interferon