{'fraction_non_alphanumeric': 0.039149888143176735, 'fraction_numerical': 0.010067114093959731, 'mean_word_length': 4.789644012944984, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Cross-talk between MGL-1 and TLR 4 abolishes LewisX-induced cross-presentation

CD8 T-cell priming is essential for the induction of strong anti-tumor responses. Therefore, it is important to target antigen to DCs, as these are the most potent APCs that can instruct CD8+ Tcells. C-type lectin receptors (CLR), expressed on APC have the ability to take up and present glycosylated antigens, but lack the capacity to mature DCs. The addition of TLR-ligands ensures DC-maturation and pro-inflammatory cytokine production. Modification of antigens with LewisX(LeX)-carbohydrate structures targets antigen to MGL1 leading to enhanced CD8+ T-cell responses and Th1-skewing of CD4+ T-helper cells. To ensure long-lasting CD8+ T-cell immunity we investigated whether LPS (TLR4-ligand) is a suitable adjuvant for OVA-LeX induced T-cell responses. Surprisingly, we found that LPS diminishes cross-presentation of LeX modified OVA, whereas CD4+ T-cell responses remained unaltered. Our data show that in this setting the uptake of OVA-LeX was not reduced. In the presence of LPS, OVA-LeX was still ingested by BMDC lacking MGL1 indicating the involvement of a second uptake receptor. In addition, we observed faster degradation of OVA-LeX than in the absence of LPS, which was paralleled by a reduction in OVA peptide-MHC class-I complexes on the DC surface. MGL1TLR4 cross-talk may affect the DC maturation status, however, we did not detect different expression of co-stimulatory molecules on OVA-LeXcompared to OVA-pulsed DCs in the presence of LPS. Yet, TNF-α production was decreased substantially. These data show for the first time that MGL1TLR4 cross talk not only affects cytokine production but may also influence antigen routing, resulting in diminished CD8+ T-cell activation. Chapter 4