Antigen recognition (9)

Question 1

How was the Major Histocompatibility complex discovered?

Answer 1

Research into graft rejection.

Question 2

What chromosome is the Major Histocompatibility complex found on in humans?

Answer 2

6.

Question 3

What can MHC also be known as in humans?

Answer 3

HLA molecules - human leucocyte antigen.

Question 4

Is the HLA-A, HLA-B or HLA-C locus most polymorphic?

Answer 4

HLA-B.

Question 5

How many alleles are there for the HLA-A locus?

Answer 5

More than 1400.

Question 6

HLA alleles are very polymorphic. How many amino acids substitutions can they differ by?

Answer 6

20 a.a.

Question 7

What type of response does the MHC complex have a major role in activating?

Answer 7

The T cell response.

Question 8

When can T lymphocytes recoginse an antigen?

Answer 8

When it is in complex with self MHC molecules.

Question 9

How were mice used experimentally to show that T cells can only recognise antigen that are bound to self MHC?

Answer 9

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.

Question 10

Does the MHCI or MHCII structure include B2-microgloblin?

Answer 10

MHCI.

Question 11

Does the MHCI or MHCII structure contain a beta chain?

Answer 11

MHCII.

Question 12

Is the MHCI or the MHCII protein completely polymorphic?

Answer 12

II.

Question 13

What part of MHCI is invariant?

Answer 13

B2- microglobulin.

Question 14

What domains of the MHC proteins are Ig like?

Answer 14

Membrane proximal domains.

Question 15

What domains of the MHC proteins bind peptide?

Answer 15

Membrane distal domains.

Question 16

Do the membrane proximal or membrane distal domains of MHC proteins contain polymorphisms?

Answer 16

Distal.

Question 17

What is the length of peptides that MHCI can bind?

Answer 17

8- 10 amino acids.

Question 18

What is the length of peptides that MHCII can bind?

Answer 18

13-25 amino acids.

Question 19

How do peptides bind to MHCI?

Answer 19

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.

Question 20

What forms the specificity pockets in the MHC proteins?

Answer 20

Polymorphic residues.

Question 21

How does MHCII bind peptides?

Answer 21

Peptide backbone interacts with invariant residues whereas side chains interact with specificity pockets found at the base of the peptide binding groove.

Question 22

The specificity pockets in MHCI and MHCII peptides are found in different places in the peptide binding groove. Where are they found?

Answer 22

In MHCI they are found at the end of the peptide binding grove whereas in MHCII they are found at the base.

Question 23

Does a particular MHC molecules bind to specific peptides or a wide range of peptides?

Answer 23

A wide range of peptides.

Question 24

What two key points regarding antigen recognition were determined by XRC?

Answer 24

1. MHC binds peptide.

2. TCR recognises complex of peptide + self MHC.

Question 25

MHC molecules have a broad specificity for peptides. What is this type of specificity also known as?

Answer 25

Degenerate specificity.

Question 26

How fast do bound peptides dissociate from MHC?

Answer 26

Very slowly.

Question 27

Where do peptides associate with MHCII?

Answer 27

Endocytic/ vesicular compartments.

Question 28

Is peptide binding essential for MHCI or MHCII cell surface expression?

Answer 28

MHCI

Question 29

What ATP driven transporter drive peptides to the ER to be associated with MHCI?

Answer 29

TAP (transporter associated with antigen presentation).

Question 30

Where are peptides produced that need to be presented via MHCII?

Answer 30

Phagolysosome.

Question 31

Where do peptides need to be processed in order to be presented via MHC1?

Answer 31

The proteosome.

Question 32

Why are co receptors needed with the TCR?

Answer 32

1. Stabilise interactions | 2. Facilitate signalling.

Question 33

What state do ITAMS have in resting cells?

Answer 33

Unphosphorylated.

Question 34

What leads to TCR ITAM phosphorylation?

Answer 34

Binding of MHC ligand to the TCR.

Question 35

What phosphorylates ITAMS in the TCR when MHC ligand binds?

Answer 35

Receptor associated tyrosine kinase.

Question 36

Once MHC ligand has bound to the TCR the TCR ITAMS are phosphorylated via a receptor associated tyrosine kinase. What happens next?

Answer 36

ZAP 70 binding to the phosphorylated signalling (zeta) domain ITAMs and is itself phosphorylated by Lck.

Question 37

What is Lck?

Answer 37

Tyrosine kinase.

Question 38

How are MHC genes expressed and why?

Answer 38

Co- dominantly in order to increase the number of different MHC molecules expressed.

Question 39

What is a major consequence of MHC polymorphism?

Answer 39

Graft rejection.

Question 40

Why is the variability of MHC molecules small compared to the variability of TCRs?

Answer 40

As all variability is inherited.

Question 41

What is MHC restriction?

Answer 41

The fact that an individuals T cell response is determined by their MHC type.

Question 42

MHC restriction means individuals can be classed into two types. What are these types?

Answer 42

Responders and non responders.

Question 43

What 6 key processes do MHC proteins function in?

Answer 43

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.

Question 44

What HLA stereotype is associated with MS?

Answer 44

DR2.

Question 45

What HLA stereotype is associated with RA?

Answer 45

DR4

Question 46

What HLA stereotype is associated with Insulin Dependant Diabetes Mellitius?

Answer 46

DR3 and DR4.

Question 47

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?

Answer 47

1. Double negative 2. Double positive 3. Single postive

Question 48

What does positive selection in thymic selection involve?

Answer 48

Removal of T cells that do not bind self MHC via apoptosis

Question 49

What does negative selection in thymic selection involve?

Answer 49

Removal of T cells that bind self MHC and self peptide via apoptosis.

Question 50

Does positive or negative selection in thymic selection occur first?

Answer 50

Postive.

Question 51

Is positive or negative selection in thymic selection most imporant?

Answer 51

Negative.

Question 52

What is it also thought MHC proteins can be involved in?

Answer 52

Mate choice.