lecture 16/17 - MHC antigen processing

Question 1

What are professional antigen presenting cells and what are their characteristics?

Answer 1

Cell that can convert the naive T cells into activated effector T cells
Dendritic cells constitutively express MHC II and costimulatory B7 molecule
Macrophages must be activated to express MHC II and B7 molecule
B cells constitutively express MHC II but must be activated to express B7 molecule

Question 2

Aside from APCs, what other cells function in antigen presentation?

Answer 2

Non professional cells, APC

Question 3

In general what steps are required for antigen recognition?

Answer 3

Production of cytosolic proteins→ proteolytic degradation of proteins → transport peptides from cytosol in ER → assembly of peptide-class I complexes → surface expression of peptide-class I complexes

Question 4

What are the steps of endogenous antigen processing and what components are necessary for its function?

Question 5

What are TAP1 and TAP2, what would happen if there was a mutation involving either gene?

Answer 5

Transporters associated with antigen processing that are located in the lumen of the ER
Contain ATP binding cassette
Mutations affect antigen presentation by MHC class I molecules, patients would show autoimmunity or chronic microbial infections

Question 6

What is the function of calnexin? How does it relate to calreticulin and Erp57 What happens after proteins are released from these proteins?

Answer 6

Stabilizes MHC class I alpha chain
Contains alpha chain in partially folded state until beta-2 microglobulin binds and forms complex
After binding to calnexin, complex binds to other chaperone proteins and tapasin
ERP57 which breaks and reforms disulfide bonds in MHC class I alpha domain during protein loading
Folded molecules exported to golgi apparatus after calreticulin is released via TAP transporter

Question 7

How do proteasomes degrade proteins

Answer 7

Ubiquitinating enzyme complex add ubiquitin to the epsilon-amino group on the lysine side chain

Question 8

What is the endocytic antigen processing pathway, in what major ways does it differ from the endogenous pathway?

Answer 8

The endosomal and lysosomal pathway
Differs because its for internalized proteins
Helper Th lymphocytes (CD4+) bind antigenic peptides whereas cytotoxic T cells (CD8+) are used for the cytosolic pathway
APCs internalize via phagocytosis or endocytosis → degradation in acidified vesicles endosomes → lysosomal fusion to form endolysosome

Question 9

Describe the process of antigen uptake and formation of vesicles, where are these taken?

Answer 9

Extracellular foreign antigens uptake into intracellular vesicles → pH decreases activating proteases

Question 10

What is the purpose of the Ii?

Answer 10

Blocks the endogenous peptides from binding to MHC class II in the endoplasmic reticulum
Later digested by enzymes in endosome leaving being a CLIP bound to the class II molecule, which prevents newly generated peptides within acidified endocytic vesicles to bind to MHC class II molecules
HLA-DM removes CLIP allowing the peptides to bind to MHC class II molecule

Question 11

What are the key points of MHC/Ag processing

Answer 11

Each MHC displays one peptide at a time bc each T cell responds to a single peptide bound to an MHC molecule
Peptides are acquired during intracellular assembly
Broad specificity because many peptides can bind to the same MHC molecule
Slow off-rate to allow bound peptides enough time to be located by the T cell