Which of the following best distinguishes MHC class II antigen presentation from MHC class I?

• A. It presents endogenous peptides to CD8+ T cells.
• B. It presents exogenous peptides to CD4+ helper T cells.
• C. It is expressed on all nucleated cells.
• D. It binds lipids for presentation to NK cells.

Answer: (B)

The key idea is that MHC class II molecules present extracellular (exogenous) peptides to CD4+ helper T cells. They are mainly on professional antigen-presenting cells (like dendritic cells, macrophages, and B cells) and sample peptides from proteins taken up from outside the cell, which are processed in endosomes/lysosomes. During this process, the invariant chain blocks the binding groove in the ER, and after trafficking to endosomes, CLIP is replaced by the actual peptide with the help of HLA-DM, allowing the peptide-MHC II complex to surface and be recognized by CD4+ T cells.

In contrast, MHC class I presents endogenous peptides from cytosolic proteins to CD8+ cytotoxic T cells. These peptides are generated in the cytosol by proteasomes, transported into the ER by TAP, and loaded onto MHC I molecules there; MHC I is expressed on nearly all nucleated cells.

The other options reflect features of MHC I or lipid presentation pathways (lipids are presented by CD1 molecules, not MHC II), so they don’t distinguish MHC II from MHC I.