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

Int J Cancer. 2011 Mar 15;128(6):1371-83. doi: 10.1002/ijc.25458.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylgalactosamine / metabolism*
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Blotting, Western
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CHO Cells
  • Cell Proliferation
  • Cricetinae
  • Cricetulus
  • Cross-Priming / immunology
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Glycosylation
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Lectins, C-Type / physiology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / physiology
  • Ovalbumin / physiology
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Histocompatibility Antigens Class I
  • Lectins, C-Type
  • MGL2 protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Ovalbumin
  • Acetylgalactosamine