Place the steps involved in processing of intracellular, cytosolic antigens in t
ID: 92158 • Letter: P
Question
Place the steps involved in processing of intracellular, cytosolic antigens in the correct chronological order. _____ MHC class I molecules progress towards the cell membrane in membrane-bound vesicles. _____ beta 2-microglobulin binds to MHC class I alpha chains. _____ MHC class I molecules bound to peptide dissociate from TAP complex. _____ Peptides are transported into the lumen of the endoplasmic reticulum using TAP proteins. _____ MHC class I complex binds to chaperone proteins (calreticulin, Erp57), tapasin, and TAP. _____ Peptides bearing the appropriate peptide-binding motif bind to MHC class I molecules and completes its folding. _____ Peptides are modified by ERAAP. _____ Cytosolic pathogens are broken down into small peptide fragments in proteasomes. _____ In the endoplasmic reticulum, misfolded MHC class I alpha chains bind to calnexin.Explanation / Answer
Major histocompatibility complex (MHC) class 1 molecules play a vital role in protecting our bodies from infection. They form the central part of host defense against viral infection.
Following infection, a virus takes advantage of protein machinery of the host for its propagation. Within the host cell, proteasome breaks down some of these viral proteins. The resulting viral peptide fragments join self-peptides. These molecules diffuse to endoplasmic reticulum (ER) where they come in contact with specialized transporters called TAP. TAP functions to transport peptide fragments from cytosol to ER lumen. In the ER, these peptides are modified with the help of ERAAP (ER-associated aminopeptidase). These peptides then bind to the key protein involved in antigen presentation of the class 1 molecule of MHC. Assembly of class 1 molecule of MHC begins with the folding of its heavy chain assisted by binding of calnexin. Calnexin stabilizes the heavy chain and prevents aggregation. Subsequent binding of beta 2 microglobulin brings about a conformational change in the heavy chain that creates a peptide-binding groove. Within this protein loading complex, calnexin is replaced by calreticulin. The remaining components of this protein loading complex are TAP transporter and tapasin. Tapasin plays a major role in stabilizing protein loading complex. It allows active binding of high affinity peptides into class 1 binding groove. This results in major confirmational change. Tapasin responds to this change which results in complete dissociation of protein loading complex. Thus, the newly formed MHC class 1 molecule proceed to the cell membrane in membrane bound vesicles.
So the steps involved in in processing of intracellular, cytosolic antigens can be summed up as:
1 Cytosolic pathogens are broken down into small peptide fragments in proteasomes.
2 Peptides are transported into the lumen of the endoplasmic reticulum using TAP proteins.
3 Peptides are modified by ERAAP (ER-associated aminopeptidase).
4 In the endoplasmic reticulum, misfolded MHC class1 alpha chains bind to calnexin.
5 Beta2 microglobulin binds to MHC class 1 alpha chains.
6 MHC class 1 complex binds to chaperone proteins (calreticulin, Erp57), tapasin and TAP.
7 Peptides bearing the appropriate peptide binding motif bind to MHC class 1 molecules and completes its folding.
8 MHC class 1 molecules bound to peptide dissociate from TAP complex.
9 MHC class 1 molecule progress towards the cell membrane in membrane bound vesicles.