Antigen Uptake, Processing and Presentation

Question 1

Self MHC Restriction of T cells

Answer 1

T cells can only recognize antigen that is presented by a self-MHC molecule
Antigen recognition by CD4+ cells is MHC2 restricted
Antigen recognition by CD8+ cells is MHC1 restricted

Question 2

Antigen presenting cells

Answer 2

Professional APCs (macrophages, B cells, dendritic cells) express MHC2 and costimulatory molecules
Non-professional APCs (skin fibroblasts and endothelial cells) can be induced to express MHC2 by IFNgamma and/or costimulatory molecules
Deliver costimulatory signals via B7 family members (CD80/86)
Dendritic cells always express MHC2 and B7, B cells express MHC2 but need to be activated for B7, macrophages need to phagocytose to express either

Question 3

B cells as poor APCs

Answer 3

Poor because they only present those that act with their antibody
Does not work before B cell stimulation when there is only small amounts of B cells with that antibody

Question 4

Activated dendritic cells

Answer 4

Go to lymph nodes to activate T cells

Question 5

Macrophage activation

Answer 5

Pattern recognition receptors and enhanced by T cell help (IFgamma)

Question 6

Target cells

Answer 6

Almost all nucleated cells (they express MHC1) can activate CD8+ cells
Except neurons

Question 7

Cytosolic antigen processing pathway

Answer 7

Processes endogenous (intracellular) antigens and presents them on the cell surface in association with MHC1
Antigens are degreased in cytoplasm into peptides (ubiquitin, proteasome)
TAP carries cytosolic peptides through RER (high affinity for 8-13aa)
Newly synthesized MHC1 alpha chain (associated with calnexin) binds to beta2 micro globulin (calnexin released) and binds with calreticulin and tapasin
ERp57 associated with complex to stabilize and releases when MHC1 has peptide
Peptide-MHC1 are transported in vesicles from RER to plasma

Question 8

Endocytic antigen processing pathway

Answer 8

Processes exogenous (extracellular) antigens and presents them on the cell membrane in association with MHC2
APCs internalize antigen by phago/endocytosis
Degraded in endosomes, endolysosomes to lysosome
MHC2 is synthesized on polysomes within RER and associated with invariant chain CD74
MHC2 travels in vesicle from RER through Golgi to complex with with endocytic compartment (invariant chain is degraded)
CLIP (remaining CD74) is replaced when MHC2 has open conformation catalyzed by HLA-DM
Entire complex is transported to plasma membrane where it adopts stable form in neutral pH

Question 9

Calreticulin

Answer 9

Molecular protein that promotes proper folding

Dissociates when ERp57 associates with MHC1 complex

Question 10

Tapasin

Answer 10

Brings TAP close to MHC1 to allow MHC1 to acquire antigenic peptide
Dissociates when ERp57 associates with MHC1 complex

Question 11

CD74

Answer 11

Invariant chain that interacts with peptide-binding cleft preventing endogenous peptides from binding with MHC2
Degraded when MHC2 enters endocytic compartment to cleave CLIP

Question 12

CLIP

Answer 12

Class 2 associated invariant chain peptide
Remains in peptide binding groove to prevent any premature binding of antigenic peptide
Exchanged to antigen, catalyzed by HLA-DM

Question 13

HLA-DM

Answer 13

Catalyzes the exchange of CLIP for antigenic peptide

Modulated by HLA-DO

Question 14

DC licensing and cross-presentation

Answer 14

Dendritic cells are able to present exogenous antigen to CTL in MHC1
Licensed by activated CD4+ helper cells