Quiz 4 Part 2 Flashcards
Explain in detail the structure of MHC Class 1
MHC class 1 consists of an alpha transmembrane chain with 3 alpha subunits
alpha 1 and alpha 2 = peptide binding domains
alpha 3 — supporting, immunoglobulin like domain
support (accessory) protein small, Ig like === beta 2 microglobulin
explain in detail the structure of MHC Class 2
has alpha and beta transmembrane chains
4 subunits total, each contributing to the peptide binding domain and supporting domains
explain where the peptide binding site is on an MHC molecule (both class 1 and class 2)
the binding site sits in a deep groove on the surface of the MHC molecule
is peptide binding to MHC covalent or noncovalent?
non-covalent forces
MHC class 1 can bind which peptides?
What about class 2?
MHC class 1 binds peptides of 8-10 amino acids (usually a 9mer)
MHC class 2 binds peptides of 13-26 amino acids
MHC molecules have a ____ binding specificity, meaning what?
PROMISCOUS
meaning that MHC molecules can bind a variety of peptides with differing amino acid sequences (derived from the degradation of pathogens)
explain the binding of TCR binding to MHC on MHC Class 1
the CD8 coreceptor on the CD8+ T cell binds to the a3 domain on MHC class 1
explain the bonding of TCR to MHC on class 2 MHC
the CD4 coreceptor in the CD4 T cell binds the B2 domain of MHC class 2
MHC class 1 molecules bind peptides in…..
the ER
MHC class 2 molecules bind peptides in….
endosomes
MHC class 1 molecules bind _______peptides in the ER
non self (derived from intracellular pathogens)
in the presence of infection, the proteasome in the cell is altered in response to…….
IFNY (secreted by NK cells)
when the proteasome is altered by IFNY, what is happening to it?
the modified proteasome processes peptides that are likely to bond to MHC Class I
the modified proteasome due to IFNY (produced by NK cells) is called……
an immunoproteasome
in the ABSENCE of infection, what is the proteasome called and what is it doing?
called a constitutive proteasome.
always actively processing SELF proteins
How are peptides transported to the ER to be recognized by MHC Class 1?
peptides are transported from the immunoproteasome to the ER by an ATP-dependent transporter protein called TAP
does TAP require ATP?
yes
where are MHC class 1 molecules assembled?
in the ER
what aids the assembly of MHC class 1 molecules?
chaperone proteins
Calnexin stables the alpha heavy chain until B-2microglobulin binds
explain the full process of MHC Class 1 binding a peptide from an intracellular pathogen
MHC Class 1 molecule is assembled. Calnexin is a chaperone protein that aids in this process by stabilizing the alpha heavy chain until B-2microglobulin binds
when the binding of b2-microglobulin to the alpha heavy chain is finished, calnexin is released.
the MHC class 1 molecule then joins the peptide loading complex consisting of 3 proteins.
a peptide is delivered by TAP (a transporter) to the class 1 heavy chain. this binding of peptide to MHC Class 1 forms the MATURE MHC CLASS 1 MOLECULE. it undergoes a conformational change
the class 1 molecule then dissociates from the peptide loading complex and is exported from the endoplasmic reticulum in a vesicle
do most peptides exhibit tight binding?
no
some peptides are ____ and some peptides are ____ to create better binding
some peptides are REJECTED and some peptides are EDITED to create better binding
what enzyme chews away the ends of peptides to reduce their size and make them fit better into MHC?
ERAP (endoplasmic reticulum aminopeptidase)
explain the process of ERAP
MHC Class 1 is loaded with peptide that is too long at the N terminus
ERAP removes N-terminal amino acids to give a peptide of 8-10 residues
MHC class 1 molecule then travels to the cell surface via a vesicle
