Supplementary Figure 4: Model of the negatively regulation of DC cross-presentation by Siglec-G.

The normal phagosomal pH helps keep an environment for low protein degradation to maintain the normal pathogen proteolysis speed, then the exogenous antigenic isotope can be recognized and loaded onto MHC class I molecules, forming a MHC class I-peptide complex and the information of exogenous antigen could be cross-presented to the CD8⁺T cells for initiation of adaptive immune response. However, at the beginning of the infection, antigens could up-regulate the expression of Siglec-G on DCs. Siglec-G on phagosomes could use the ITIM domain to recruit SHP1 which dephosphorylates p47^phox, the subset of NOX2, and consequently inhibits NOX2 activation and ROS production. So the pH of phagosomes drops and the levels of proteolysis rise, high proteolysis and low pH destroy MHC class I-restricted epitopes. As a result, Siglec-G impairs the formation of the MHC class I–peptide complex and CD8α⁺DC cross-presentation, finally inhibiting the initiation of adaptive immune response.