Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Int J Cancer. 2011 Mar 15;128(6):1371-83. 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.
我们最近表明，MGL2 特异性结合肿瘤相关糖基 N-乙酰半乳糖胺（GalNAc）。在这里，我们证明了用肿瘤相关糖基 GalNAc 修饰抗原，可以将抗原特异性靶向骨髓来源（BM）-DC 和脾 DC 上的 MGL2。用模拟肿瘤相关糖基化的 GalNAc 修饰抗原，促进了 DC 内的抗原内化和呈递给 CD4 T 细胞，以及 IFN-γ产生的 CD4 T 细胞的分化。此外，GalNAc 修饰的抗原增强了 BM-DC 和原代脾 DC 的交叉呈递，导致抗原特异性 CD8 T 细胞反应增强。使用 MyD88-TRIFF(-/-) BM-DC，我们证明 GalNAc 修饰抗原的增强交叉呈递与 TLR 无关。我们的数据强烈表明，肿瘤相关 GalNAc 修饰的抗原靶向 DC 上的 MGL，并以 TLR 独立的方式极大地增强 MHC 类 II 和类 I 的呈递。
