MHC class 1 is expressed in ..?
All nucleated cells
MHC class2 is expressed in …?
professional APCs
What domain of MHC class 2 binds CD4?
beta domain
What domain of MHC class 1 binds CD8?
alpha domain
TCR binds both the antigen and MHC molecule. True or False?
True
Which of MHC Class-1 and Class-2 has a relatively closed groove so the binding occurs in pockets at the ends of the groove?
Class-1
Describe the MHC class-2 antigen binding groove.
The groove is much more open so can accommodate bigger peptides and bind all along the length of the binding site.
Where are peptides for MHC class-2 derived from?
Extracellular peptides.
(MHC-2 Synthesised in cell, translocate to ER, vesicles bud off and bind with peptides in antigen-processing compartment)
Where are peptides for MHC class-1 derived from?
Intracellular peptides.
Often from when a cell is infected with a virus.
Where are viral antigen broken down for presentation on MHC class-1?
proteasome (peptide then binds to class 1 molecule in golgi and transported to surface.)
What does interferon-gamma turn the proteasome into?
The immunoproteosome.
This contains additional subunits.
What additional subunits does immunoproteosome contain that proteasome doesn’t?
LMP2, LMP7, MECL1
These change specificity of cleavage.
What is the difference in function between immunoproteosome and proteasome?
There is an increased cleavage after hydrophobic residues so there are more peptides with C terminal hydrophobic residues which favours binding to MHC class 1.
What is TAP?
Transporter for antigen processing. Transport degraded peptides from proteasome to endoplasmic reticulum
What does Calnexin do?
Stabilises MHC class 1 heavy chain until beta-globulin binds and releases calnexin.
In the endoplasmic reticulum what is the function of the chaperone proteins that interact with the MHC class 1?
Interact with MHC class I to hold it in open configuration so peptides can bind. They then dissociate.
When a MHC class-1 molecule is loaded with a peptide that has too long an N-terminus what cleaves the peptide?
ERAP - an aminopeptidase
What cleaves the invariant chain from the MHC class-2?
cathepsin S cleaves invariant chain forming CLIP (class-2 associated invariant peptide)
What is the molecule that facilitates the release of CLIP called?
HLA-DM
Is the Li-MHC 2 transported to the antigen processing compartment intact?
Yes
What is the rare event cross-presentation?
When macrophages ingest an infected cell and degrade it. Peptides of the infected cells enter the endoplasmic reticulum and form MHC I complexes and are presented on the outside
What is the major histomcompatibility complex?
A cluster of genes associated with antigen processing and presenting. This codes for the MHC molecules
What is the histomcompatibility complex called in humans?
HLA (human leukocyte antigen)
What is the histomcompatibility complex called in mice?
H2 complex
Each MHC will have more than one major locus. True or False?
True
In the example given there were 3, in fact there are more than this. As you have two chromosomes complexity is increased.
Why is your complement of MHC unique to you?
These gene regions are highly polymorphic
Why is it important to type donor tissue in transplant?
Otherwise cytotoxic T cells will recognise MHC class I on transplanted organ as foreign and will amount an immune respond against it.
Why are differences in our alleles retained in the population?
Heterozygosity is an advantage.
Certain alleles are associated with resistance to specific diseases. If we had the same sets a pathogen could and knock out a species.
New MHC alleles are generated by …?
Interalleic conversion between the same or different genes.
B27 gives you a WHAT fold risk of developing Ankylosing spondylitis?
90
which part of the TCR binds the peptide?
CDR3
which part of the TCR binds the MHC?
CDR1 and CDR2
