Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses.
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.
Singh
Satwinder Kaur
SK
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Streng-Ouwehand
Ingeborg
I
Litjens
Manja
M
Kalay
Hakan
H
Saeland
Eirikur
E
van Kooyk
Yvette
Y
D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D010047:Ovalbumin / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015295:Antigens, Tumor-Associated, Carbohydrate; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D000116:Acetylgalactosamine