Block A - lecture 2 Flashcards

1
Q

what is the part of the T cell that recognises the antigen ?

A

the T cell receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what chains make up the TCR ?

A

an alpha and a beta chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

are the chains always constant or variable and explain

A

There is a variable beta and a variable alpha chain. The constant regions do not change in sequence from T cell to cell and they are located closer to the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

how do the variable regions form ?

A

The variable regions are deliberately mutated to generate variants so that it could fit a range of antigen and peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

are the variable regions in T cells all the same or different ?

A

the variable regions in an individual of T cell are all the same , however each T cell generates its own particular variable region. So that you have a series of different T cells. Within each T cell there are thousands of receptors and they are all the same

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what do the TCR share similarities with ?

A

the immunoglobin domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the MHC class II molecule on and what does it present to ?

A

on the presenting cell , not the T cell. It contains the peptide and presents it to the T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

where does the TCR lie and what does it contain that recognises the peptide from the APC?

A

Within the bilayer, the T cell receptor lies and it contains the alpha and beta chains and this is what recognises the peptide from the APC. The peptide will be complimentary in shape to the receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how come the T cell doesn’t contain a signalling capacity and as a result what causes the signalling ability ?

A

It does not contain tails that extend into the cytosol and it doesn’t have a signalling capability as a result of this. The T cell receptor and accessory proteins that are involved in signalling surround the receptor and collectively called the T cell receptor complex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

explain the CD3 complex ?

A

A major part of the complex that is closest to the binding site is called the CD3 complex chains and they lie to the right. They consist of 4 peptide chains that are labelled as Epsilon, delta and gamma, there are 3 different types of chains. The epsilon chain surrounds the delta and gamma chains to form a tetrameric complex. This CD3 complex interacts with 2 further chains called zeta chains that are free within the membrane of the inactivated T cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

explain the CD4 marker proteins ?

A

In addition to the zeta chains, there is CD4 marker proteins to the left which contains the receptor binding site for the MHC molecule. So that when the APC, containing the MHC class II arrives, the peptide binds to the T cell receptor and the CD4 proteins bind to the MHC class II.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

explain the location of the LCK molecule and it’s function ?

A

It is attached to CD4 but not covalently is a protein called LCK, it is a kinase (add phosphates) and found on the inner bilayer of the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CD45 ?

A

CD45 is found in the membrane and it is an enzyme, a phosphatase (removes phosphates).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

ITAMS?

A

ITAMS (immunoreceptor Tyrosine Activation Motifs) these are motifs or patterns that are commonly recurring in a variety of proteins when it comes to signalling. They are common in immune cells. The motifs are the recurring pattern and the amino acid is what is recurring. This is important as tyrosine signalling is occurring and it is the phosphorylation of tyrosine using a kinase ( adding a phosphate) or phosphatase ( removing a phosphate) that affects signalling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

in the ITAMS , what is the Y and L showing ?

A

Y is the code name for tyrosine, and this is separated by 2 amino acids and then leucine ( L). Then between 6 to 8 intervening amino acids then repeated of the tyrosine and 2 amino acids separated them from leucine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the role of the ITAM’s ?

A

An ITAM’s job is to interact with the SH2 and SH3 regions which are sark homology regions. The sark means they are like a protein called src which is a kinase , involved in cancer cells and normal physiological functions.

17
Q

explain SH2 ?

A

SH2 region is 100 amino acid long on the protein and it has a tyrosine phosphate docking region , so that it can dock with tyrosine but only if a phosphate is present

18
Q

explain SH3 ?

A

SH3 region is shorter at 60 amino acids and interacts with proline rich regions.

19
Q

src protein family ?

A

Src protein family kinases have a SH2 ( tyrosine- phosphorylated docking) and SH3 region ( proline docking) as well as a kinase catalytic cabability and with this there’s a regulatory area.

20
Q

syk protein ?

A

Syk protein kinases do not have SH3 regions , instead 2 SH2 regions , they contain a catalytic domain which doesn’t have a regulatory sub unit.

21
Q

what are the Syk and src kinases regulated by ?

A

regulated by a phosphorylated tyrosine within the catalytic domain. Src kinases has a phosphorylated tyrosine which modulates the regulatory portion.

22
Q

what does the phosphorylated tyrosine on ITAM’s allow the Sh2 regions of proteins with src homology allow ?

A

proteins with src homology region 2 to dock onto the phosphorylated tyrosine. The SH2 region will not dock unless the ITAMS are phosphorylated as a result of some activation event.

23
Q

does the Lck interact with ?

A

CD4

24
Q

is it embedded into the membrane ?

A

nope , it hangs out , not embedded

25
Q

what kinase family is Lck kinase part of ?

A

Lck kinase is a src family protein as it contains a SH3 and SH2 component , catalytic domain and a regulatory sub unit

26
Q

what post translational modification is found on lyk and what does this allow ?

A

On amino acid number 2 there is a C14 unit and a fatty acid myristic acid covalently bound to the protein as a post translational modification. It is this fatty acid that allows lyc to interact with the membrane and keep it anchored.

27
Q

what is lyc kinase controlled by ?

A

The kinase is controlled by a phosphorylation of the tyrosine which is amino acid 394

28
Q

what is the regulatory component that controls the kinase activity ?

A

The regulatory component that controls the kinase activity is itself controlled by the amino acid 505.

29
Q

what is the inactive state of lyc kinase ?

A

the inactive state , the amino acid 505 has a phosphorylated tyrosine and it is in the pocket of an SH2 region. This covers the catalytic domain , so when 505 tyrosine is phosphorylated it is in an inactive state.

30
Q

active state of lyc kinase ?

A

The phosphorylated tyrosine is removed by a phosphatase (CD45), this allows the lck kinase to open up and it is ready to carry out catalytic function on a target protein. The regulatory domain is also regulated by a phosphorylation , the amino acid 394 needs to be phosphorylated for it to carry out catalytic activity. This phosphorylation is carried out by numerous kinases , it isn’t just one.

31
Q

what is the key step lyc kinase activation ?

A

The key step is the de-phosphorylation of amino acid 505 as this allows the protein to open up and the regulatory domain can become phosphorylated.

32
Q

what is the receptor for MHC class II

A

CD4

33
Q

what occurs when the CD4 binds to the MHC class II?

A

ThWhen the CD4 binds to the MHC class II this enhances the binding between the peptide and TCR. The CD4 and associated lck then moves closer to the TCR and this is the most important step in activation of the TCR. It is dependent on not just a ligand but how the various components in the membrane are brought together through spacial proximity. The lck kinase phosphorylates the tails of CD3 which penetrate the cytoplasm ,the tails contain ITAMS. is phosphorylation of the CD3 tails allows the zeta chains to come into close contact and the lck kinase can phosphorylate the chains of zeta.

34
Q

what occurs after the phosphorylation of the zeta chains?

A

After the phosphorylation of the zeta chains this allows ZAP-70 (zeta associated protein kinase 70) to dock to the ITAM’s. It is a kinase, and this phosphorylates target proteins such as phospholipase C – gamma one. The LAT protein is an adaptor, and this allows the interaction of ZAP 70 with PLC. The APC with MHC class II carrying a peptide in binding cleft , binds to TCR , this allows binding of CD4 and lck close to the complex of CD3 , and the tails are phosphorylated which leads to phosphorylation of PLC gamma one. These steps occur in the T cell membrane.

35
Q

wher do these steps occur ?

A

in the T cell membrane