MHC Loading

Question 1

MHCI Antigen Processing & Loading

Answer 1

Intracellular microbe protein goes through proteasome → generates peptides that are carried by TAP1/2 into the ER → peptides (9 AAs) are then loaded onto MHCI in ER → peptide/MHC complex is then transported to the surface of the APC via exocytosis

Question 2

MHCII Antigen Processing & Loading

Answer 2

MHCII binds invariant chain in ER (keeps it from picking up endogenous peptides) → MHCII/invariant chain complex leave ER through Golgi-packed endosomes → endosome and phagosomes w/ extracellular material fuse → endosome enzymes chop up pathogen protein into antigenic peptides and degrade invariant chain so that only CLIP is remaining in MHCII groove → HLA-DM catalyzes release of CLIP from MHCII groove → Antigenic peptide is now loaded onto MHCII → MHCII/peptide complex is transported to the APC surface via exocytosis

Question 3

Cross Presentation

Answer 3

= Antigens taken up from outside the cell are loaded onto and presented by MHCI molecules

Important because some viruses impair DC fxn by inhibiting MHC class I-restricted presentation, which would prevent MHCI presentation to CTLs.

Immune system gets around this by having uninfected DCs take up antigen from infected cells (extracellular to these DCs) and present them on MHCI to CTLs.