Test 3: T cell antigen processing

Question 1

Which MHC molecule displays peptides that are processed via the Endocytic pathway vs Cytosolic Pathway?

Answer 1

MHC I: Cytosolic

MHC II: Endocytic

Question 2

Can exogenous substances be presented by Class I MHCs?

Answer 2

Yes–on dendritic cells

Question 3

What makes up the 26s proteasome?

Answer 3

20s core: substrate proteolysis

19s regulator complex: recognizes ubiquinated substrate and unfolds

Question 4

What are the steps of the cytosolic pathway?

Answer 4

• cytosolic protein ubiquinated
• ubiquinated protein targeted and unfolded by proteasome
• proteasome degrades protein (longer segments when INF-gamma present)
• peptide transported from cytosol to ER where it binds to MHC I
• MHC I with protein transported to golgi–>surface of cell

Question 5

What transports the protein from the cytosol to the ER? Is it active or passive transport?

Answer 5

Transporter Associated with Antigen Processing (TAP) molecule; ACTIVE

Question 6

What are immature dendritic cells called and where are they located?

Answer 6

Langerhans Cells in skin and mucosal surfaces

Question 7

What cytokine increases expression of MHC IIs on macrophages?

Answer 7

Gamma interferon

Question 8

Which APCs capture and transport antigens from lymph and blood?

Answer 8

Phagocytic mononuclear cells and B cells

Question 9

What APCs capture epithelial/mucosal antigens?

Answer 9

Langerhans cells–>inflammation–>migration of langerhans to lymph nodes–>loss of phagocytic property, gain of MHC II molecules–>in lymph node, expression of CCR7=Dendritic cells

Question 10

Steps of endocytic pathway

Answer 10

• endocytosed antigen may fuse with lysosome to be degraded
• MHC II made on RER of phagosome with Invariant chain (Ii) attached
• Invariant chain has CLIP sequence bound to binding cleft of MHC II
• MHC II vesicle fuses with peptide vesicle
• Invariant chain cleaved by proteolytic enzymes and CLIP removed
• peptide binds with MHC II and travels to cell surface

Question 11

What molecule removes the CLIP from the binding cleft of MHC II?

Answer 11

HLA-DM (higher affinity than for the cleft)

Question 12

What is the function of HLA-DO?

Answer 12

inhibits activity of HLA-DM; dissociates once antigen is internalized by B cell

Question 13

What antigens are displayed by CD-1 molecules?

Answer 13

Microbial and self Lipids

Question 14

What is the origin of most peptides displayed by MHC molecules?

Answer 14

Self peptides