T lymphocyte and antigen recognition

Question 1

What is the general structure of a T Cell Receptor?

Answer 1

It consists of an alpha and beta chain

Both chains have a variable region and a constant region

Question 2

What other receptor are TCRs associated with and how does it transmit signals?

Answer 2

CD3 is present on all T lymphocytes and they have a longer cytoplasmic tail than the TCR
Signals from the TCR are transmitted to the internal compartment of the cell via the CD3 receptors
The tails of CD3 have tyrosine residues
When antigen binds to the TCR, phosphorylation of tyrosine occurs in the tails, which leads to many chemical cascades.

Question 3

What class of MHC do CD4+ T cells bind to?

Answer 3

MHC Class II

Question 4

What class of MHC do CD8+ T cells bind to?

Answer 4

MHC Class I

Question 5

What type of cells are CD4+ T cells? What do they do?

Answer 5

T helper cells – T helper 1 cells are involved in inflammatory responses (activate macrophages) whereas T helper 2 cells are involved in B cell activation

Question 6

What type of cells are CD8+ T cells? What do they do?

Answer 6

Cytotoxic T lymphocytes – kills virus infected cells

Question 7

Where are immature thymocytes found in the thymus?

Answer 7

In the cortex – mature thymocytes are found in the medulla

Question 8

Describe, in full, T cell development in the thymus.

Answer 8

T cells initially have no TCR or CD4/CD8 receptors
The beta chain of the TCR assembles first followed by the alpha chain
If the TCR is functional, the T cell goes on to express both CD4 and CD8 receptors
Depending on which MHC class it binds to it eventually ends up being only CD4+ or CD8+

Question 9

What do CD4 and CD8 bind to?

Answer 9

They bind to the side of the MHC molecule

Question 10

In what order does gene rearrangement take place?

Answer 10

Beta chain is rearranged first (VDJ recombination) and then the alpha chain (VJ recombination)

Question 11

What percentage of thymocytes survive selection?

Answer 11

5%

Question 12

Describe, in full, the structure of MHC Class I.

Answer 12

MHC Class I consists of a heavy alpha chain which is polymorphic and a beta-2 microglobulin chain which is the same in everyone
Only the alpha chain has a transmembrane domain

Question 13

How does the light polypeptide associate to the heavy polypeptide in MHC Class I?

Answer 13

Non-covalent bonding

Question 14

What part of MHC Class I is transmembrane?

Answer 14

Alpha chain

Question 15

Describe, in full, the structure of MHC Class II.

Answer 15

MHC Class II consists of two polypeptides of a similar size, an alpha and a beta chain
Both chains have a transmembrane domain

Question 16

What part of MHC Class II is transmembrane?

Answer 16

Both the alpha and beta chains have transmembrane domains

Question 17

What is the difference between the types of peptides presented by Class I and Class II?

Answer 17

Class I presents peptides that are smaller than the MHC molecule
Class II presents peptides that are longer than the MHC molecule so it often has bits protruding out of the MHC molecule

Question 18

Describe how the structure of MHC allows it to bind to a broad variety of peptides.

Answer 18

It has a binding motif that consists of binding pockets where you get particular amino acids binding in those positions – this is a feature that is conserved in most peptides

Question 19

What is the name for the Human MHC region in the genome?

Answer 19

Human Leukocyte Antigen

Question 20

What are the types of MHC Class I genes?

Answer 20

A, B and C

Question 21

What are the types of MHC Class II genes?

Answer 21

DP, DQ, DR

Question 22

How many types of MHC molecule can one person produce?

Answer 22

12 – 6 class I and 6 class II

Question 23

What is an MHC haplotype?

Answer 23

Group of MHC alleles linked together on a single chromosome

Question 24

Describe the process of antigen presentation via MHC Class I.

Answer 24

MHC Class I present endogenous antigens
Viral proteins are processed by a proteasome and move through TAP protein into the ER
In the ER, the MHC Class I molecule assembles and a chaperone protein aids its folding
Once it has fully assembled, it can move to the cell surface via the golgi apparatus

Question 25

Describe antigen presentation via MHC Class II.

Answer 25

Antigens are endocytosed and move into the endocytic pathway.
Newly formed MHC Class II molecules enter the ER using a signal sequence
In the ER, the MHC Class II associates with an invariant chain (blocks the binding site to make sure molecules that are meant to be loaded onto MHC Class I aren’t loaded onto class II.)
The invariant chain has a signal sequence that directs the MHC towards the endocytic pathway.
As it moves into the endocytic pathway, the invariant chain is digested leaving only a clip protein.
The final step is the replacing of the clip protein by the antigen.