Flashcards in Antigen recognition (9) Deck (52):
How was the Major Histocompatibility complex discovered?
Research into graft rejection.
What chromosome is the Major Histocompatibility complex found on in humans?
What can MHC also be known as in humans?
HLA molecules - human leucocyte antigen.
Is the HLA-A, HLA-B or HLA-C locus most polymorphic?
How many alleles are there for the HLA-A locus?
More than 1400.
HLA alleles are very polymorphic. How many amino acids substitutions can they differ by?
What type of response does the MHC complex have a major role in activating?
The T cell response.
When can T lymphocytes recoginse an antigen?
When it is in complex with self MHC molecules.
How were mice used experimentally to show that T cells can only recognise antigen that are bound to self MHC?
Two inbred mice ( A and B) are immunized with virus B however only T cells from mouse A can kill infected A cells as T cells from B to not recognise A's self molecules.
Does the MHCI or MHCII structure include B2-microgloblin?
Does the MHCI or MHCII structure contain a beta chain?
Is the MHCI or the MHCII protein completely polymorphic?
What part of MHCI is invariant?
What domains of the MHC proteins are Ig like?
Membrane proximal domains.
What domains of the MHC proteins bind peptide?
Membrane distal domains.
Do the membrane proximal or membrane distal domains of MHC proteins contain polymorphisms?
What is the length of peptides that MHCI can bind?
8- 10 amino acids.
What is the length of peptides that MHCII can bind?
13-25 amino acids.
How do peptides bind to MHCI?
The N and C termini bind to the invariant pockets at the end of the peptide binding groove via two or three anchor residues found on the peptide itself.
What forms the specificity pockets in the MHC proteins?
How does MHCII bind peptides?
Peptide backbone interacts with invariant residues whereas side chains interact with specificity pockets found at the base of the peptide binding groove.
The specificity pockets in MHCI and MHCII peptides are found in different places in the peptide binding groove. Where are they found?
In MHCI they are found at the end of the peptide binding grove whereas in MHCII they are found at the base.
Does a particular MHC molecules bind to specific peptides or a wide range of peptides?
A wide range of peptides.
What two key points regarding antigen recognition were determined by XRC?
1. MHC binds peptide.
2. TCR recognises complex of peptide + self MHC.
MHC molecules have a broad specificity for peptides. What is this type of specificity also known as?
How fast do bound peptides dissociate from MHC?
Where do peptides associate with MHCII?
Endocytic/ vesicular compartments.
Is peptide binding essential for MHCI or MHCII cell surface expression?
What ATP driven transporter drive peptides to the ER to be associated with MHCI?
TAP (transporter associated with antigen presentation).
Where are peptides produced that need to be presented via MHCII?
Where do peptides need to be processed in order to be presented via MHC1?
Why are co receptors needed with the TCR?
1. Stabilise interactions
2. Facilitate signalling.
What state do ITAMS have in resting cells?
What leads to TCR ITAM phosphorylation?
Binding of MHC ligand to the TCR.
What phosphorylates ITAMS in the TCR when MHC ligand binds?
Receptor associated tyrosine kinase.
Once MHC ligand has bound to the TCR the TCR ITAMS are phosphorylated via a receptor associated tyrosine kinase. What happens next?
ZAP 70 binding to the phosphorylated signalling (zeta) domain ITAMs and is itself phosphorylated by Lck.
What is Lck?
How are MHC genes expressed and why?
Co- dominantly in order to increase the number of different MHC molecules expressed.
What is a major consequence of MHC polymorphism?
Why is the variability of MHC molecules small compared to the variability of TCRs?
As all variability is inherited.
What is MHC restriction?
The fact that an individuals T cell response is determined by their MHC type.
MHC restriction means individuals can be classed into two types. What are these types?
Responders and non responders.
What 6 key processes do MHC proteins function in?
1. Graft rejection.
2. Antigen presentation to T cells.
3. T cell activation.
4. Self/ non self recognition.
5. Autoimmune disease.
6. Development of T cell repertoire in the thymus.
What HLA stereotype is associated with MS?
What HLA stereotype is associated with RA?
What HLA stereotype is associated with Insulin Dependant Diabetes Mellitius?
DR3 and DR4.
T cells undego thymic selection. What states is the T cell present in in the thymus before it leaves the thymus to enter the peripheral lymphoid tissue?
1. Double negative
2. Double positive
3. Single postive
What does positive selection in thymic selection involve?
Removal of T cells that do not bind self MHC via apoptosis
What does negative selection in thymic selection involve?
Removal of T cells that bind self MHC and self peptide via apoptosis.
Does positive or negative selection in thymic selection occur first?
Is positive or negative selection in thymic selection most imporant?