Adaptive Immune System- Antigen Processing and Presentation

Question 1

What is the major histocompatibility complex (MHC)?

Answer 1

A complex of genes that are major determinants of tissue compatibility during transplantation. Used to present antigen fragments to T cells and bind T cell receptors

Human: HLA
Mouse: H-2

Question 2

What are the three types of MHC Class 1?

Answer 2

HLA-A, HLA-B, HLA-C

Question 3

Give the expression of MHC Class 1

Answer 3

All nucleated cells in the body, APCs, platelets. Not on RBCs.

Question 4

Give the function of MHC Class 1

Answer 4

Alerts CD8+ cytotoxic T cells to intracellular antigens

OR

Present endogenously synthesized antigens to CD8+ cytotoxic T cells

Question 5

Give the structure of MHC Class 1

Answer 5

1 long chain, 1 short chain

Arranged as B C A

Question 9

Give the structure of MHC class 2

Answer 9

2 equal length chains (2 α, 2 beta)

Arranged DP, DQ, DR

Question 10

What is encoded within the MHC Class 3 region?

Answer 10

C4, Factor B, C2, Lymphotoxin, TNF α

Question 11

Which features of MHC Class are what varies from one individual to another?

Answer 11

2 α-helices and beta sheet floor varies from one individual to another band between the different MHC molecules

Question 12

What are non-polymorphic regions on the MHC important for?

Answer 12

The binding of other molecules to MHC (CD8 on 1, CD4 on 2)

Question 13

What are pMHC?

Answer 13

Peptide MHC

Question 14

A cell was destroyed by the immune system using the performing-granzyme pathway. What class of MHC is most likely to have signaled this T cell? How do you know?

Answer 14

MHC Class 1, because MHC 1 binds to CD8 on cytotoxic T cells

Question 15

Give the function of MHC Class 2

Answer 15

Alerts CD4+ helper T cells and regulatory T cells to extra cellular antigens

OR

Present exogenously synthesized antigens to CD4+ helper T cells

Question 16

Give the expression of MHC Class 2

Answer 16

Present on professional APCs (dendritic cells, macrophages, B cells) and on thymic epithelium

Question 17

What are the three types of MHC Class 2?

Answer 17

HLA-DP, HLA-DQ, HLA-DR

Question 18

Which human chromosome has the MHC?

Answer 18

Chromosome 6, inherited from mother

Question 19

Which MHC chain is essentially non-polymorphic?

Answer 19

HLA-C β chain

Question 20

Which sequence does not vary between individuals?

Answer 20

The HLA class 1 β chain gene

Question 21

What is the associated protein of MHC Class 1?

Answer 21

β-2 microglobulin

Question 22

In the MHC Class 1, which domains are polymorphic?

Answer 22

The α-1 and α-2 domains of the α chain.

Question 23

Which MHC class 1 domain is closest to the transmembrane sequence?

Answer 23

The α3 domain

Question 24

Which part of the MHC Class 1 molecule maintains the correct structural conformation of the α β heterodimer but doesn’t function in peptide binding?

Answer 24

β2- microglobulin

Question 25

Which 2 locations can an antigen come from?

Answer 25

Endogenous
-processing of these antigens produce peptides that are 8-9 amino acids long
(MHC Class 1)

Exogenous
-processing of these antigens produce peptides that are approximately 15 amino acids long
(MHC Class 2)

Question 26

What is TAP (TAP1 and TAP2)

Answer 26

Transporters associated with Antigen Processing

They pick up peptides as they’re being fed out of the end of the immunoproteasome and take them across the ER

Question 27

What is the difference between the constitutive protein and the immunoproteasome?

Answer 27

The immunoproteasome is specialized to produce peptides of the length required to bind into MHC Class 1 groove

Question 28

What do Tapasin, Calreticulin and Erp57 do?

Answer 28

They help keep the conformation of the MHC Class 1 correct for peptide binding

Question 29

What is the molecule: invariant chain (Ii)

Answer 29

Acts as a stopper to prevent binding in the ER to the MHC Class 2

Question 30

What is the remaining part of the invariant chain called?

Answer 30

CLIP

Question 31

What does DM and DO do?

Answer 31

They remove CLIP and insert the peptide into the peptide binding groove

Question 32

Why is ubiquitination an important part of antigen processing?

Answer 32

It marks the protein so that the proteasome can recognize it

Question 33

A patient has a functional genetic defect in the area of a genome that encodes for the TAP1 and TAP2 molecules. At a molecular level, what would this patients cells not be able to do?

Answer 33

Transport processed peptides out of the cytosol, through the ER, to be presented by the MHC Class 1 molecule

Question 34

Discuss cross presentation

Answer 34

The endogenous and exogenous pathways are not completely separated.
Endogenous antigens can enter the MHC Class 2 and be presented to CD4+ helper and regulatory T cells.
Exogenous antigens can enter the MHC Class 1 and be presented to CD8+ cytotoxic T cells

Question 35

When does the term cross presentation apply?

Answer 35

Exogenous antigens are presented by MHC Class 1