1. During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a
ID: 204072 • Letter: 1
Question
1. During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a ‘peptide receptive’ state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing
ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide
editing is important to the immune response because it:
A. Maintains high levels of surface MHC class I expression
B. Ensures that MHC class I molecules are not degraded in the ER
C. Retains the nascent MHC class I molecule in a peptide
receptive state
D. Allows surface MHC class I molecules to bind new peptides
from the extracellular milieu
E. Prevents surface MHC class I molecules from undergoing
peptide exchange at the cell surface
2. True/False: MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
3. Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells.
B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
C. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein.
D. Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn’t replicate in dendritic cells.
E. No, because the type I interferon response induced by the virus infection will up-regulate MHC class I expression and override the immune evasion mechanism.
Explanation / Answer
Ans. 1 Peptide editing is important as it protects the MHC class 1 molecule to exit ER qua;ity control and ensuring proper exit. Hence it ensures that MHC class I molecules are not degraded by ER. Therefore the correct option is option B.
Ans. 2 The given statement is true the MHC class I molecule needs a peptide for bounding derived from pathogen. In case its abscence the MHC class I molecule would be remaining in the ER which would be then transferred back to cytosol for degradation.
Ans 3. The correct option is option A Yes as no viral peptide : MHC complexes to activate CD 8 T cells. The invading virus would encode proteins which functions as ligands for binding to the complexes resulting in the non binding of MHC class I molecules to bound with the peptide.
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