Tumour‐associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses

• Published in: International journal of cancer Vol. 128; no. 6; pp. 1371 - 1383
• Main Authors: Singh, Satwinder Kaur, Streng‐Ouwehand, Ingeborg, Litjens, Manja, Kalay, Hakan, Saeland, Eirikur, van Kooyk, Yvette
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2011; Wiley-Blackwell
• Subjects: Acetylgalactosamine - metabolism; Animals; Antigen presentation; Antigen Presentation - immunology; Antigens, Tumor-Associated, Carbohydrate - immunology; Biological and medical sciences; Blotting, Western; Bone marrow; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Cross-Priming - immunology; Data processing; Dendritic cells; Dendritic Cells - immunology; Differentiation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; glycans; Glycosylation; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Interferon; Lectins, C-Type - physiology; Lymphocyte Activation; Lymphocytes T; Major histocompatibility complex; Medical sciences; MGL2; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Differentiation Factor 88 - physiology; N-Acetylgalactosamine; Ovalbumin - physiology; Polysaccharides; Receptors, Antigen, T-Cell - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Spleen; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Tumors; Modification; Antigen presentation; HLA-System; Immune response; Tumor associated antigen; MGL2; Major histocompatibility system; Glycan; Cancerology; glycans; Histocompatibility restriction; Macrophage galactose-type C-type lectin; Class I histocompatibility antigen; CD8 T lymphocyte
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.25458

We recently showed that MGL2 specifically binds tumour‐associated glycan N‐acetylgalactosamine (GalNAc). We here demonstrate that modification of an antigen with tumour‐associated glycan GalNAc, targets antigen specifically to the MGL2 on bone marrow derived (BM)‐DCs and splenic DCs. Glycan‐modification of antigen with GalNAc that mimics tumour‐associated glycosylation, promoted antigen internalisation in DCs and presentation to CD4 T cells, as well as differentiation of IFN‐γ producing CD4 T cells. Furthermore, GalNAc modified antigen enhanced cross‐presentation of both BM‐DCs and primary splenic DCs resulting in enhanced antigen specific CD8 T cell responses. Using MyD88‐TRIFF−/− BM‐DCs we demonstrate that the enhanced cross‐presentation of the GalNAc modified antigen is TLR independent. Our data strongly suggest that tumour‐associated GalNAc modification of antigen targets MGL on DCs and greatly enhances both MHC class II and class I presentation in a TLR independent manner.