T-Lymphocytes and Antigen Recognition

Question 1

What do T lymphocytes monitor?

Answer 1

The inside of cells

Question 2

Describe the structure of the TCR. What are the subsets.

Answer 2

Related to the Fab part of an antibody. Has a variable, constant and transmembrane region as well as a cytoplasmic tail. Has alpha and beta components but a small subset use gamma and delta (10%).

Question 3

What molecule is present on EVERY T lymphocyte?

Answer 3

CD3

Question 4

Key difference between CD3 polypeptide and the TCR?

Answer 4

CD3 polypeptide has a much longer cytoplasmic tail

Question 5

What happens when the T cell receptor meets its antigen regarding the CD3 polypeptide?

Answer 5

The tails have motifs containing tyrosine residues and when the TCR receptor meets its antigen phosphorylation of the tyrosine occurs

Question 6

Do both types of T cells secrete cytokines?

Answer 6

Yes

Question 7

What do T helper 1 target and are involved is?

Answer 7

Involved in inflammatory responses, activates macrophages to kill phagocytosed material

Question 8

What are T helper 2’s involved in?

Answer 8

Activation of a B cell

Question 9

Are immature thymocytes found in the centre or outside of the thymus?

Answer 9

Towards the outside

Question 10

Describe the maturation of the T cell. What do precursors lack when they reach the thymus? Which chain rearrangement takes place first? How are CD4/CD8 expressed?

Answer 10

When the precursors arrive at the thymus, they have NO TCR, CD4 or CD8. Rearrangement of the gene segments for the beta chain takes place and then the alpha chain to form the TCR. Then CD4 and CD8 are expressed (double positive). There is a selection process to see which kind of MHC molecule the cell can recognise, either CD4 by binding to an MHC class II molecule or CD8 aka MHC class I.

Question 11

How is the beta chain rearranged in the TCR (which components)?

Answer 11

VDJC (remember C is constant region)

Question 12

How is the alpha chain rearranged in the TCR (which components)?

Answer 12

VJC (remember C is constant region)

Question 13

How many variable gene segments in the TCR?

Answer 13

5

Question 14

What needs to be checked to ensure a TCR is functioning? (2)

Answer 14

See if it recognises MHC, makes sure it doesn’t bind too tightly to MHC.

Question 15

What % of thermocytes survive selection?

Answer 15

5%

Question 16

What is the structure of MHC I?

Answer 16

Heavy alpha chain, with three domains (2 in the peptide binding region, 1 in Ig like region) and light beta 2 microglobulin chain.

Question 17

Is the alpha chain polymorphic?

Answer 17

Yes

Question 18

Is the beta 2 microglobulin chain polymorphic?

Answer 18

No

Question 19

Is the beta 2 microglobulin chain transmembrane?

Answer 19

No

Question 20

What is the structure of MHC II?

Answer 20

Alpha and beta chains of equal size that are both transmembrane

Question 21

Where do peptides bind in MHC II,

Answer 21

Between alpha 1 and beta 1

Question 22

Which MHC class presents at longer peptides?

Answer 22

MHC class II

Question 23

What is an MHC binding motif?

Answer 23

The way MHC can present many different peptides but with some specificity. Certain positions tend to be particular amino acids and others could be anything else

Question 24

What HLA?

Answer 24

Human MHC

Question 25

What are the three types of class I MHC?

Answer 25

A B and C

Question 26

What are the three types of class II?

Answer 26

DP, DQ and DR

Question 27

What chromosome is the HLA genes found on?

Answer 27

6

Question 28

Is beta 2 microglobulin found on the same chromosomes as the HLA genes?

Answer 28

No

Question 29

How many different class I and II molecules can we make and why?

Answer 29

6 of each as we are diploid and the HLA genes are codominant.

Question 30

Which cells express MHC class I and which express class II?

Answer 30

All nucleated cells express I, and only professional APC's have class II

Question 31

What is the most polymorphic gene in the human body? What are the consequences of this?

Answer 31

MHC. This means that we all have different responses to the same infection.

Question 32

What produces endogenous antigens? How are these presented? Which MHC class presents them?

Answer 32

Virus's. Viral proteins are processed by a multisubunit proteolytic system - proteasome. Peptides then move into the ER via TAP (transporter associated with antigen processing). MHC class I moves into ER. The alpha chain binds with the peptide and the beta 2 microglobulin. Then goes via the Golgi to the cell surface.

Question 33

What produces exogenous antigens? How are these presented? Which MHC class presents them?

Answer 33

Proteins are endocytosed and processed into peptides in endocytic vesicles. Class II molecules enter ER, and associates with the invariant chain. The invariant chain is the digested as the complex enters the endocytic pathway. You end up with a small peptide fragment bound to MHC II known as CLIP (Class II Associated Invariant Chain Peptide). The CLIP peptide is then swapped for the antigenic peptide. Peptide and MHC II then goes to cell surface.

Question 34

What is the purpose of CLIP?

Answer 34

Stops peptides that should be going onto class II going onto class I.