TCR and MHC molecules

Question 1

What are the two major T-cell sub population?

Answer 1

CD4+ T-cells:
- Helper T-cells, TH-cells
CD8+ T-cells:
- Cytotoxic T-lymphocytes, (CTL)

Question 2

What do T-cells express on their surface apart from TCR and what is it responsible for? (2)

Answer 2

CD3
Responsible for signalling

Question 3

What are the principles of antigen recognition by T-cells? (4)

Answer 3

Antigen is recognised by the T-cell receptor (TCR)

Antigen is presented to T-cell by second cell - this cell functions as an antigen presenting cell (APC)

Antigen is presented by MHC molecules on the APC cell surface

Antigen is not native but is instead processed: proteins are processed by proteases into peptide fragments

Question 4

What is the difference between the role of MHC class I and class II molecules? (2)

Answer 4

MHC class II molecules present antigens to CD4+ T-cells

MHC class I molecules present antigens to CD8+ T-cells

Question 5

Describe the structure of a T cell receptor (4)

Answer 5

Integral membrane protein that is anchored to the surface of a T cell

Two chains held together by disulphide bond

Each chain has a variable and constant domain

The two variable domains combine to form the antigen recognition site

Question 6

What is CD3? (3)

Answer 6

Component of TCR complex

Transduce a signal when TCR interacts with antigen causing T cell to become activated

Question 7

What are T-cell epitopes? (4)

Answer 7

T cells recognise short contiguous peptides, typically 8 to 12 amino acids in length

Not possible to co-crystallise TCR and epitope as with antibodies and their antigens

Studies of the crystal structure of MHC molecules, short amino acid peptide co-crystallised in a “cleft”

Functional assays of T-cells, revealed that they only respond to short contiguous peptides

Question 8

What can be the possible structure of antigen? (2)

Answer 8

Can be from anywhere in the folded structure of a protein, ie can be either surface exposed or buried within the folded structure of the protein

Question 9

How to identify a T cell epitope in an antigen? (5)

Answer 9

Antigen, APC incubated with T cell clone

This produces a response

Synthesise overlapping
peptides representative
of complete sequence

Test each epitope
individually for
T-cell response

Epitope
identified

Question 10

What is MHC class I antigen presentation important for? (1)

Answer 10

Important in immune response to viruses and cancer

Question 11

Where are MHC class I molecules expressed? (1)

Answer 11

MHC class I molecules are expressed on the cell surface by all nucleated cells

Question 12

Function of MHC class I molecules (2)

Answer 12

Present intracellular (endogenous) antigens from within the antigen presenting cell eg viral proteins and tumour antigens

Question 13

Describe the MHC class I antigen presentation pathway (3)

Answer 13

Virus synthesise their own proteins
Viral proteins chopped up by proteasome to produce peptides
These are translocated in lumen of endoplasmic reticulum and loaded onto MHC class I molecules which present the antigen

Question 14

Where are MHC class II molecules expressed? (2)

Answer 14

Expressed on the cell surface of ‘professional’ antigen presenting cells: B-cells, dendritic cells and macrophages

Question 15

Function of MHC class II molecules (2)

Answer 15

Present extracellular (exogenous antigens) that are taken up by endocytosis from outside of the cell

Question 16

Describe the MHC class II antigen presentation pathway (5)

Answer 16

Antigen taken up by endocytosis and delivered into endosomes where it is chopped up into peptide fragments by proteases

MHC molecule associated with invariant chain
This traffics newly synthesised MHC molecules to endosomes

It is then chopped up itself and therefore, opens up peptide binding site for antigenic peptide to bind

MHC molecules loaded with peptides derived from antigen
Displayed on cell surface

Question 17

Compare MHC class I and II presentation (5)

Answer 17

Check one note:
MHC and TCR lecture

Question 18

Describe structure of MHC class I molecules (3)

Answer 18

Expressed on the plasma membrane
MHC molecules have 4 extracellular domains, 2 of which form the peptide binding site
MHC class I molecules comprise the heavy chain and beta-microglobulin

Question 19

Describe structure of MHC class II molecules (3)

Answer 19

Expressed on the plasma membrane
MHC molecules have 4 extracellular domains, 2 of which form the peptide binding site
MHC class II molecules comprise the alpha and beta chains

Question 20

What are MHC molecules in terms of genes? (1)

Answer 20

Polygenic: there is more than one gene for the MHC class I and MHC class II molecules
Alleles expressed Co dominantly expressed

Question 21

What is the major histocompatibility Complex (MHC) (4)

Answer 21

Complex of genes encoding for proteins involved in immunity
Class I region codes for MHC class I heavy chains HLA-A, -B, & -C (HLA: human leukocyte associated)
Class II region codes for MHC class II molecules HLA-DR, -DP & -DQ
Class III codes for some complement proteins and some cytokines

Question 22

Why are MHC molecules polygenic and polymorphic? (3)

Answer 22

Each MHC molecule can bind and present a distinct repertoire of antigenic peptides to T-cells

By expressing up to 6 MHC class I and 6 MHC class II molecules we increase the number of different peptides we can present to T-cells

There are millions of different combinations of MHC alleles: makes it difficult for pathogens to evolve their protein sequences to prevent the presentation of their antigens

Question 23

How and why can MHC molecules cause problems in transplation? (4)

Answer 23

Mismatched MHC molecules make tissues and
organs histoincompatible
The successful transplantation of organs or bone marrow is more likely when MHC molecules are
closely matched between donor and recipient
Mismatched MHC transplants are more likely to be
rejected
Ideal donors for transplants are identical twins
(100% matched MHC)