Lecture 7 - MHC and Antigen Presentation to T Cells

Question 1

Differentiate between the different types of T helper cells (CD4+).

L7 S4-5

Answer 1

Th1:

• produce IFN-γ to activate Mφ
• activate cytotoxic T cells
• respond to intracellular microbes

Th2:

• produce IL-4 to stimulate B cell proliferation
• induce B cell development into memory cells and plasma cells
• respond to extracellular microbes

Question 2

What are TCRs?

L7 S6-7

Answer 2

T-cell receptor

• found on membrane of T-cells
• two polypeptide chains (α and β) with constant and variable regions
• recognize ONLY LINEAR polypeptide sequence presented by MHC molecules

Question 3

What are the functional differences of the different classes of MHC molecules?
What T cell type recognizes each class?

L7 S10

Answer 3

MHC class I:

• found on all nucleated cells and present intracellular microbes
• encoded by genes HLA-A, -B, and -C)
• polymorphic, large α-chain and nonpolymorphic, small β-chain
• recognized by CD8+ (cytotoxic T cells)

MHC class II:

• found only on APCs (B cells, DCs, and Mφ) and present extracellular microbes
• encoded by gene HLA-DP, -DR, and -DQ
• equally sized polymorphic α-chain and polymorphic β-chain
• recognized by CD4+ (helper T cells)

Question 4

What types APCs/MHC II expressing cells are there?
What cytokine increases the MHC II present on the cell?
What class of T cell does the APC interact with

Answer 4

DC:

• IFN-γ (MHC II already present but stimulates increase)
• naïve T cell activation

Mφ:

• IFN-γ (MHC II not already present and is induced)
• effector T cell response

B cell:

• IL-4 (MHC II already present but stimulates increase)
• effector T cell response

Question 5

What cell type is responsible for producing IFN-γ and what causes it to do so?
What is the function of IFN-γ and how does this relate to the self limitation of the immune response?

L7 S26

Answer 5

Natural killer cells secrete IFN-γ during their function in innate immune response and helper T cell (CD4+) secrete it in response to being resented antigen by APCs.

IFN-γ is a survival factor for Mφ and DCs. In the absence of IFN-γ the cells undergo apoptosis. It also stimulates MHC II expression on Mφ and increase expression on DCs.

Question 6

What are the main routes of pathogen entry?
What cells are primarily responsible for capturing these antigens and where are they located or where do they take the antigens?

L7 S24

Answer 6

Skin, gastrointestinal tract, and respiratory tract:
-captured by DCs and taken to lymph nodes

Blood:
-taken to spleen by circulation and captured by APCs in the spleen

Question 7

What changes occur to a DC when it captures an Ag?

L7 S25

Answer 7

• loss of expression of Fc receptors and mannose receptors
• gain of expression of ICAM-1 and IL-12 (T cell activators)
• increase in half-life of MHC II molecules and increase in MHC II molecules

Question 8

What is the class I MHC pathway?

L7 S29

Answer 8

• cytosolic pathogen produces protein (all nucleated cells) or phagocytized protien (APCs)
• protein is targeted for degradation and is degraded
• peptides are transported to ER where MHC class I is present
• peptide-MHC class I complex is assembled
• complex is transported to cell membrane via Golgi and secretory vesicle
• MHC class I complex presents antigen to cytotoxic T cell (CD8+)

Question 9

What is the class II MHC pathway?

L7 S30

Answer 9

• extracellular protein is uptaken via endocytic vesicle
• protein is processed/degraded in endosomal/lysosomal vesicles
• MHC class II is independently synthesized and processed in ER and Golgi respectively
• MHC class II vesicle fuses with endosome and peptide-MHC class II complex is assembled
• vesicle fuses with cell membrane and MHC class II complex presents antigen to helper T cell (CD4+)

Question 10

What is the class I MHC pathway?

L7 S29

Answer 10

• cytosolic pathogen produces protein
• protein is targeted for degradation and is degraded
• peptides are transported to ER where MHC class I is present
• peptide-MHC class I complex is assembled
• complex is transported to cell membrane via Golgi and secretory vesicle
• MHC class I complex presents antigen to cytotoxic T cell (CD8+)

Question 11

What is the class II MHC pathway?

L7 S30

Answer 11

• extracellular protein is uptakes via endocytic vesicle
• protein is processed/degraded in endosomal/lysosomal vesicles
• MHC class II is independently synthesized and processed in ER and Golgi respectively
• MHC class II vesicle fuses with endosome and peptide-MHC class II complex is assembled
• vesicle fuses with cell membrane and MHC class II complex presents antigen to helper T cell (CD4+)

Question 12

What is the function of HLA-DM and what process is it used in?

L7 S31-32

Answer 12

HLA-DM is used in the MHC class II pathway to aid in peptide loading of MHC class II.

Functions:

• dissociation of CLIP (protein involved in assembly and staization of MHC class II) from MHC class II
• prevents degradation of empty MHC class II
• facilitates binding of Ag

Question 13

What is the function of HLA-DM and what process is it used in?

L7 S31-32

Answer 13

HLA-DM is used in the MHC class II pathway to aid in peptide loading of MHC class II.

Functions:

• dissociation of CLIP (protein involved in assembly and staization of MHC class II) from MHC class II
• prevents degradation of empty MHC class II
• facilitates binding of Ag