Describe the process and purpose of antigen presentation via MHC I versus MHC II.

• A. MHC I presents exogenous peptides to CD4+ T helper cells; MHC II presents endogenous peptides to CD8+ cytotoxic T cells.
• B. MHC I presents endogenous peptides to CD8+ T cells; MHC II presents exogenous peptides to CD4+ T helper cells.
• C. MHC I presents endogenous peptides to CD4+ T helper cells; MHC II presents exogenous peptides to CD8+ T cells.
• D. MHC I presents peptides to B cells; MHC II presents peptides to NK cells.

Answer: (C)

Antigen presentation by MHC molecules guides which T cell arm gets activated. MHC I handles endogenous peptides, meaning proteins produced inside the cell (such as viral proteins), and it presents these to CD8+ cytotoxic T cells. These peptides are generated in the cytosol by the proteasome, transported into the endoplasmic reticulum by TAP, loaded onto MHC I there, and then the peptide–MHC I complex travels to the cell surface for recognition by CD8+ T cells, which are equipped to kill infected cells.

MHC II, on the other hand, handles exogenous peptides from proteins that come in from outside the cell. Professional antigen-presenting cells like dendritic cells, macrophages, and B cells take up these extracellular proteins, process them in endosomes/lysosomes, and load the resulting peptides onto MHC II in those compartments. The peptide–MHC II complex is then presented on the cell surface to CD4+ helper T cells, which orchestrate broader immune responses by helping activate other immune cells, including B cells and cytotoxic T cells.

This pairing—endogenous peptides with CD8+ T cells and exogenous peptides with CD4+ T cells—drives the distinct roles of cell-mediated cytotoxic responses and helper-driven orchestration of the immune response.