Fig 1.
Prions fail to activate B cells with or without T cell help.
A simplified model of T cell-dependent and independent B cell activation. Binding of antigen to IgM on the surface of B cells provides the first activation signal. (A) T cells that recognize antigen processed by the B cell and presented in MHC II molecules provide the second signal, typically through its CD40 ligand binding CD40 on the B cell during infections with classic pathogens. (B) Prion-specific T cells are absent during prion infection. Other innate immune receptors, like CD21 or TLRs, can provide secondary signals without T cells in response to (C) bacteria, but not to (D) prions.
Fig 2.
Antigen processing and presentation of classic pathogens and prions.
A simplified model showing a macrophage processing and presenting viral (A) and prion (B) antigens. Each panel depicts typical antigen processing of (1) exogenous pathogens via endocytosis and fusion with acidified lysosomes, which degrade proteins into small peptides. Endolysosomes then fuse to vesicles containing MHC II molecules, which load peptides into their antigen binding clefts. Vesicles containing loaded MHC II molecules traffic to and fuse with the plasma membrane, depositing the loaded MHC II molecule on the cell surface. (2) Ubiquitin chains mark endogenous pathogens for degradation by the proteosome, which process proteins into peptides. Multiple proteins, including TAP and Calreticulin, help load peptides onto MHC I molecules and transport them to the cell surface. (3) Autophagy can degrade cellular proteins derived from the host and pathogens into peptides that can be presented by MHC I molecules. Cross presentation of (4) endogenous pathogens by MHC II and (5) exogenous pathogens by MHC I molecules via processing through the autophagosome and the proteosome occur less frequently. Prions likely constipate antigen processing at multiple points in these pathways, preventing presentation of prion-specific antigens.