Question 7 of 20 Fundamentals Concept
What do MHC class I and class II molecules present, and to which T cells?
Short answer
MHC class I sits on almost every nucleated cell and shows peptides from proteins made inside the cell to CD8 cytotoxic T cells. MHC class II is found mainly on antigen-presenting cells such as dendritic cells, macrophages and B cells, and shows peptides from material taken up into endosomes to CD4 helper T cells.
Why
The split matches two kinds of threat. A virus replicating inside a cell makes its proteins in the cytosol. Fragments are carried into the endoplasmic reticulum, loaded onto class I and displayed, so any infected cell can be recognized and killed by a CD8 T cell.
Bacteria and toxins outside cells are taken up by antigen-presenting cells and broken down in endosomes. Class II molecules fold with a protein called the invariant chain, which blocks the groove until they reach those compartments. There a fragment called CLIP is exchanged for a pathogen peptide with the help of HLA-DM, and the complex activates CD4 T cells that coordinate the response.
CD8 and CD4 bind the nonpolymorphic parts of class I and class II respectively, which is why the pairing is so strict. In humans, class I is HLA-A, B and C and class II is HLA-DR, DP and DQ, all highly polymorphic. That polymorphism decides which peptides a person can present, which matters for vaccine design and for predicting immunogenicity of biologics.
The rule has an exception. Some dendritic cells cross-present external antigen on class I, which is how CD8 responses to tumors and some vaccines arise.
A strong answer covers
- Class I on nucleated cells, class II mainly on antigen-presenting cells
- Class I shows internally made peptides to CD8 T cells
- Class II shows endosomal peptides to CD4 T cells
- Invariant chain, CLIP and HLA-DM in class II loading
- HLA polymorphism shapes the peptides presented
Common mistakes
- Saying class II is expressed on all nucleated cells
- Pairing CD8 T cells with class II molecules
- Ignoring cross-presentation when explaining CD8 responses to external antigens
The interviewer might ask next
How does cross-presentation let a dendritic cell prime a CD8 response to a tumor antigen?