T lymphocytes 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 which is attached to a short (alpha and beta have SHORT) cytoplasmic tail.
A small subset uses gamma and delta chains

Question 2

What class of MHC do CD4+ T cells bind to?
What class of MHC do CD8+ T cells bind to?

What is the consequence of co-receptors binding to MHC

Answer 2

CD4+ MHC II
CD8+ MHC I
These co-receptors bind to the MHC and increase the avidity (the overall strength of binding between an antibody and an antigen.) of T cell- target cell interaction and are important in signalling.

Question 3

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

Answer 3

T helper cells:

• Secretes cytokines
• Recruit effector cells- activate macrophages
• help and activate Cytotoxic T cells and B cell responses

Question 4

What other receptor are T Cell Receptors associated with and how does it transmit signals?

Answer 4

CD3 is present on all T lymphocytes and they have a longer cytoplasmic tail than the TCR alpha and beta chains.
The tails have motifs containing tyrosine residues. When the TCR meets its antigen: phosphorylation of Tyrosine in the motifs occur.
This triggers several other chemical cascades.
ITAM- Immunoreceptor Tyrosine-based Activation Motif
therefore CD3 is important to send signals to the lymphocyte.

Question 5

Which part of the TCR interacts with the antigen. What causes the diversity in this region

Answer 5

Variable region.

Caused by gene segment recombination.

Question 6

What is important about CD3 polypeptides?

Answer 6

They are important in the delivery of the signal to the T lymphocyte once the antigen has been recognized.
They can also be used as markers for T lymphocytes.

Question 7

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

Answer 7

Cytotoxic T lymphocytes –

• kill target cells
• induce apoptosis in target cells

Question 8

What are CD4 and CD8 and what do they bind to? What do TCR bind to?

Answer 8

CD4 & CD8 are co-receptors that bind to the side of the MHC molecule.
TCR bind to the antigen presented by the MHC

Question 9

Describe in detail what CD8+ Cytotoxic T cells do?

Answer 9

• Viral infected cells have viral proteins which are processed and presented on MHC class I for recognition by CD8+
• TCR binds to the MHC and the CD8+ binds to the side of the MHC

Question 10

What do CD4+ Th1 do?

Answer 10

• Involved in inflammatory responses

- activates the macrophages so they can kill phagocytosed material.

Question 11

What do CD4+ Th2 do?

Answer 11

• Important in helping B cell responses
• it captures the antigen on the b cell receptor and takes up the antigen
• the antigen is processed and fragments are processed on the MHC class II.
• Th2 binds and activates the B cell so it starts producing a response

Question 12

Describe the cycle of thymus

Answer 12

• Progenitor cells move from the bone to the Thymus
• They begin as immature thymocytes in the cortex
• as they develop they move towards the medulla- becoming Mature thymocytes

Question 13

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

Answer 13

• T cells initially have no TCR or CD4/CD8 receptors.
• Rearrangement of the gene segments takes place to form the antigen specific receptor.
• 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 14

In what order does gene rearrangement take place and how does this achieve diversity?

Answer 14

Beta chain is rearranged first (VDJ recombination) and then the alpha chain (VJ recombination)
-Diversity is achieved by randomly selecting from the gene segments available

Question 15

What percentage of thymocytes survive selection?

Answer 15

5%

Question 16

Define MHC

Answer 16

A group of tightly linked genes that are important in specific immune response

Question 17

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

Answer 17

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.

• Non-covalent between the light chain (beta-2 microglobulin) and the alpha chain
• peptides bond between the alpha-1 and alpha-2 domains.

Question 18

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

Answer 18

Non-covalent bonding

Question 19

What part of MHC Class I is transmembrane?

Answer 19

Alpha chain

Question 20

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

Answer 20

MHC Class II consists of two polypeptides of a similar size, an alpha and a beta chain Both chains have a transmembrane domain
Peptide binds between alpha-1 and beta-1.

Question 21

What part of MHC Class II is transmembrane?

Answer 21

Both the alpha and beta chains have transmembrane domains

Question 22

Describe the differences in how the peptides bind in Class I and class II

Answer 22

Class I- Peptides bind between the alpha-1 and alpha-2 domains.
class II- peptides bind between alpha-1 and beta-1

Question 23

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

Answer 23

Class I- present peptides that are shorter

Class II- present longer peptides, this means it often sticks out of the peptide-binding site on the MHC

Question 24

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

Answer 24

It has a binding motif that consists of binding pockets where you get particular amino acids binding in those positions.
the other positions could allow any other amino acids to bind.
This allows MHC to present a subset of peptides, which have some things in common where characteristics are conserved

Question 25

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

Answer 25

Human Leukocyte Antigen

Question 26

What are the types of MHC Class I genes?

What are the types of MHC Class II genes?

Answer 26

A, B and C = codes for only the heavy chains.

DP, DQ, DR

Question 27

How many types of MHC molecule can one person produce?

Answer 27

12 – 6 class I and 6 class II

Question 28

Does MHC only contain of Class i and class II?

Answer 28

No, 40% of the genes contain immune related function

Question 29

Describe the features of MHC

Answer 29

• Polygenic - there are several class I and class II loci
• Codominant- maternal and paternal genes are expressed
• MHC I: nearly all cells - expression varies during infection or by cytokines
• MHC II: only on professional APCs- regulated by cytokines. MHC class II linked to autoimmune disease

Question 30

Describe the process of antigen presentation via MHC Class I.

Answer 30

MHC Class I present endogenous antigens.
Viral proteins are processed by a proteasome and move through TAP (transporter associated with antigen processing) protein into the ER.
In the ER, the MHC Class I molecule assembles and  chaperone protein associates which aids its folding. The class I heavy chain binds to the peptide and B2-microglobulin.
Once it has fully assembled, it can move to the cell surface via the golgi apparatus- this only happens if all 3 are correctly folded.

Question 31

Describe antigen presentation via MHC Class II.

Answer 31

MHC class II present exogenous antigens.
Proteins are endocytosed and processed into peptides in endocytic vesicles. 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 (stops peptides that need to be loaded on MHC I from being 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 (class II associated Invariant Chain Peptide) protein. The final step is the replacing of the clip protein for the antigenic peptide.
Then the antigenic peptide is then loaded onto MHC class II ad moves to the cell surface for recognition by CD4 T cells.

Question 32

What are the types of APC’s?

And what are their locations?

Answer 32

• Dendritic cells : Widely spread e.g skin and mucosal tissue
• B lymphocytes: Lymphoid tissue
• Macrophages (Activated): Lymphoid Tissue

Question 33

what is MHC haplotype?

Answer 33

Group of MHC alleles linked together on a single chromosome.