Sara - MHC Binding, Polymorphism and Processing

Question 1

How many different Class I molecules can an individual express?

Answer 1

Up to 6 different types

Question 2

How many different Class II molecules can an individual express?

Answer 2

12

Question 3

Describe the peptide binding to MHC
(4)

Answer 3

It is not highly specific

Unlike antibodies or T cell receptors

The MHC must be able to present a huge array of antigens to T cells

MHC undergoes promiscuous binding

Question 4

What is meant by promiscuous binding

Answer 4

The ability of MHC to bind multiple different antigens and present them to T cells

Question 5

What is the ideal length of a peptide for Class I?

Answer 5

9 amino acids long (between 8 and 10)

Question 6

What happens if a longer peptide binds to the groove of MHC Class I?

Answer 6

It can be cleaved in the endoplasmic reticulum by exopeptidases

Question 7

Give an example of an exopeptidase

Answer 7

ERAp

Question 8

Give an example of an exopeptidase

Answer 8

ERAP

Question 9

What does the MHC peptide require during peptide binding?

Answer 9

The peptide must contain specific amino acid residues:

• at the amino and carboxy termini
• at positions 2 and or 3 and 9

Question 10

What does histocompatibility determine?

Answer 10

Determines whether cells in a tissue are seen as self or not

Question 11

What is the region that codes for MHC in mice called?

Answer 11

The H2 region

Question 12

What does MHC class III do?
(2)

Answer 12

Produces TNFa

Produces heat shock proteins

Question 13

How many Class I molecules can be produced from a chromosome 6?

Answer 13

Three class I molecules

Question 14

What must be done to antigens in order for MHC to use them?

Answer 14

The antigens must be processed into peptides -> between 8 and 10 amino acids long for Class I

Question 15

What type of peptide fragments are generally used for Class I?

Answer 15

Endogenous peptide fragments

Question 16

What type of peptide fragment are generally used for Class II?

Answer 16

Exogenous peptides

Question 17

What is meant by an endogenous peptide and how are they processed?
(4)

Answer 17

A viral peptide -> virus uses cell’s biological machinery to make it’s viral proteins inside (endogenous) the cell

Immunoproteosome enzymic subunits breaks these proteins down into peptides

Transporter associated with antigen processing (TAP) shuttles peptides to ER

MHC complex made and sent to cell surface via golgi apparatus

Question 18

Where does MHC loading take place?

Answer 18

In the Endoplasmic reticulum

Question 19

What is meant by exogenous peptides and how are they loaded into MHC Class II?
(4)

Answer 19

APC engulfs a bacteria (exogenous)

Phagosome and lysosome = phagolysosome

Bacterial peptides brought to ER for loading

MHC Class II expressed on surface of APC

Question 20

Name the alleles that code for MHC alpha chain

Answer 20

B, C and A

Question 21

What is the cytosolic pathway of antigen processing

Answer 21

The loading of MHC Class I molecules with endogenous peptides

Question 22

In the endogenous pathway of antigen presentation in MHC Class I, what breaks down viral peptides?

Answer 22

Immunoproteosome enzymic subunits breaks these proteins down into peptides

Question 23

What does TAP stand for?

Answer 23

Transporter associated with antigen processing

Question 24

How is the immunoproteasome shaped?

Answer 24

Barrel shaped

Question 25

How can B cells undergo antigen presentation?

Answer 25

Via receptor mediated endocytosis (not phagocytosis)

Question 26

During the processing stage, what is the main difference between the endogenous and exogenous presentation of peptides?

Answer 26

In the exogenous pathway, after phagocytosis/endocytosis the MHC Class II is sent to the membrane bound vesicle containing the peptide (CD74 tells the MHC where to go)

Question 27

List the three MHC Class I molecules

Answer 27

HLA-B, HLA-C, HLA-A

Question 28

Where do the alpha and beta chains of MHC Class II come form?

Answer 28

Coded by alleles on the short arm of chromosome 6 (other end to the MHC Class I)

Question 29

Describe the alleles that code for MHC Class II a and B chains?

Answer 29

They are both polymorphic genes (unlike MHC Class I)

Question 30

How many regions are there to the alpha chain of MHC Class I?

Answer 30

2 regions (a1, a2)

Question 31

How many regions are there to the B chain of the MHC Class II?

Answer 31

Two regions (B1, B2)

Question 32

What is the preferred peptide size for MHC Class II?

Answer 32

13-18 amino acids

Question 33

Why can only some cells express MHC Class II?
(3)

Answer 33

MHC Class II presents antigens to Helper T cells (CD4+)

Helper T cells are responsible for releasing a lot of cytokines to trigger other cells

If all cells could express MHC Class II we would have a cytokine storm and die

Question 34

What are the three alleles that code for the alpha and beta chains of MHC Class II?

Answer 34

DB, DQ, DR (each of these loci code for an alpha and a beta chain)

Question 35

How many class II molecules can you have?

Answer 35

12