Where is the antigen loaded for MHC-I and MHC-II?

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Study for the NBME Immunology Test. Study with flashcards and multiple choice questions, each question includes hints and explanations. Prepare to excel!

Multiple Choice

Where is the antigen loaded for MHC-I and MHC-II?

Explanation:
Antigen loading for MHC class I happens in the endoplasmic reticulum. Newly made MHC-I molecules associate with beta2-microglobulin and, after proper folding, bind peptides that are transported into the ER by TAP from cytosolic proteasomal degradation. This peptide loading stabilizes the MHC-I complex, which then travels to the cell surface to present to CD8+ T cells. For MHC class II, loading occurs later in the endosomal/lysosomal pathway, specifically in acidified compartments. In the ER, MHC-II binds the invariant chain, which blocks the peptide-binding groove and directs the complex to endosomes. In these compartments, the invariant chain is degraded to CLIP, and specialized processes (involving HLA-DM) promote exchange of CLIP for antigenic peptides. The loaded MHC-II-peptide complex then moves to the cell surface to present to CD4+ T cells. So the best description is that MHC-I loads peptides in the rough endoplasmic reticulum, while MHC-II loads peptides in acidified endosomes after the invariant chain is removed.

Antigen loading for MHC class I happens in the endoplasmic reticulum. Newly made MHC-I molecules associate with beta2-microglobulin and, after proper folding, bind peptides that are transported into the ER by TAP from cytosolic proteasomal degradation. This peptide loading stabilizes the MHC-I complex, which then travels to the cell surface to present to CD8+ T cells.

For MHC class II, loading occurs later in the endosomal/lysosomal pathway, specifically in acidified compartments. In the ER, MHC-II binds the invariant chain, which blocks the peptide-binding groove and directs the complex to endosomes. In these compartments, the invariant chain is degraded to CLIP, and specialized processes (involving HLA-DM) promote exchange of CLIP for antigenic peptides. The loaded MHC-II-peptide complex then moves to the cell surface to present to CD4+ T cells.

So the best description is that MHC-I loads peptides in the rough endoplasmic reticulum, while MHC-II loads peptides in acidified endosomes after the invariant chain is removed.

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